Primate basal ganglia system
Encyclopedia
The basal ganglia
form a major brain system in all species of vertebrates, but the basal ganglia of primates (including humans) have special features that justify a separate consideration. As in other vertebrates, the primate basal ganglia can be divided into striatal, pallidal, nigral, and subthalamic components. In primates, however, the two pallidal subdivisions are called the external and internal (or sometimes lateral and medial) segments of the globus pallidus
, whereas in other species they are called the globus pallidus and entopeduncular nucleus. Also in primates, the striatum is divided by a large tract of white matter called the internal capsule
into two masses of gray matter that early anatomists named the caudate nucleus
and putamen
-- in most other species no such division exists, and only the striatum as a whole is recognized. Beyond this, the complex topography of connections between the striatum and cortex means that functions are segregated within the primate striatum in ways that do not apply to other species.
A separate consideration of the primate basal ganglia is also warranted by the fact that different types of information are available than for other species. Large areas of the primate brain are devoted to vision; consequently the role of the basal ganglia in controlling eye movements has been studied almost exclusively in primates. Functional imaging
studies have been performed mainly using human subjects. Also, several major degenerative diseases of the basal ganglia, including Parkinson's disease
and Huntington's disease
, are specific to humans, although "models" of them have been proposed for other species.
, about the same size as the corticopontine system opening the cerebellar system
. The corticostriatal connection represents a significant portion of the whole cortical output. Almost every part of the cortex, except for the primary olfactory, visual and auditory cortices, sends axons to the striatum. The origin of the connection is in the pyramidal neurons of layer V of the cortex. Corticostriate contributors, of the motor cortex at least, may be collaterals of axons descending lower in the nervous system. However, in primates, the majority of corticostriate axon
s are monotarget, purely cortico-striate, thin and unbranched until they arrive in the striatum
. The corticostriatal connection is glutamatergic and excitatory. This connection is not topologically as simple as was initially described by Kemp and Powell (1970), where the frontal lobe
projected anteriorly and the occipitotemporal lobes
posteriorly. Part of this distribution grossly remains, but the distribution is much more complex. One small cortical site can send terminal arborisations to several and distal striatal places. The cortico-striatal connection is the substrate of cortical information separation and recombination: axons from distinct cortical areas can systematically end together or separately. There is also a spatial reorganisation, a "remapping"(Flaherty and Graybiel, 1991).
The corticostriate connection is the first in a chain of strong reduction in numbers between emitter and receiver neurons, i.e. a numerical convergence. The effect of this is that if each striatocortical neuron has its own message, this will be mixed or compressed, leading to lesser definition of the input map.
is the main element of the basal ganglia system. It consists in a huge neuronal telencephalic
subcortical mass.
arborisations of the spiny neurons are spherical unless close to a border. Their overall dimensions depend on the animal species. Spines are of the same type as those of two other (telencephalic) acanthodendritic (acanthos means spine) genera, the pyramidal neurons of the cerebral cortex and the spiny neurons of the amygdala
. Most of these spines synapse with cortical afferents. The axons of spiny neurons have abundant and dense initial axonal collaterals acting fast on neighbouring neurons. The distal part is long and myelinated. The spiny neurons are GABAergic, constituting the first part of the inhibitory 2-path so particular to the system . The leptodendritic neurons (or Deiter's) stain for parvalbumin
and have all the morphological properties of pallidal neurons. The spidery neurons are specific to primates. They have a big soma and short dendritic and axonal branches. They are the cholinergic
neurons of the primate, with a morphology entirely different from that of non-primates. This must lead to great care in making physiopathological transfers. They are the "tonically active neurons" or TANs. The microneurons are local circuit neurons similar to those found in the thalamus for instance. They are GABAergic, and some may be dopaminergic
.
core includes the striatum and its direct targets, reached through the striato-pallidonigral bundle: the two nuclei of the pallidum and the substantia nigra
.
s (following another one on the rat) has drastically changed the situation. Spiny neurons, generally, have several targets. This is not an archaic pattern since it is found in 90% of the cases in macaque monkeys versus 63,6% in the rat. Virtually all striatal axons have the lateral pallidum (the most voluminous) as their first target. 24/27 of the studied axons projected to the three consecutive targets, lateral pallidum, medial pallidum and nigra (lateralis and reticulata). There are no striatal axons projecting to the medial pallidum alone, to the nigra alone or only to both. Between matricial and striosomal axons, the only difference in axonal hodology
is that striosomal axons cross the whole lateral to medial extent of the nigra and emit (in macaques) 4 to 6 vertical collaterals, forming vertical columns entering deep inside the pars reticulata. The matricial neurons emit more sparsely branched axons. This general pattern of connectivity raises new problems. The main mediator of the striato- pallidonigral system is GABA
, but with cotransmitters. The lateral pallidum stains for met-enkephalin
, the medial for substance P
and/or dynorphin
and the nigra for both. This likely means that a single axon is able to concentrate different comediators in different subtrees depending on the target. This considerably modifies several decades-old schemes and raises new questions.
The synaptology of the set is uncommon and characteristic. The dendrites of the pallidal or nigral axons are entirely covered by synapses, without any apposition of glia. More than 90% of synapses are of striatal origin. One noticeable property of this ensemble is that not one of its elements receives cortical afferents.
Initial collaterals are present. However, in addition to the presence of various appendages at the distal extremity of the pallidal neurons that could act as elements of local circuitry, there are weak or no functional interrelations between pallidal neurons.
(GPe). It is flat, curved and very extended (parasagittally and dorsoventrally). The three-dimensional shape of arborisations is discoid and flat. The arborisations are parallel to one another and to the lateral border of the pallidum. They are perpendicular to the striatal afferences. In addition to the striato-pallidal afference, the lateral pallidum receives a major connection from the subthalamic nucleus (see below). It also receives dopaminegic afferences from the nigra compacta.
Contrary to two other elements of the basal ganglia core, the lateral pallidum is not a source of output to the thalamus as it sends its axons essentially to other basal ganglia elements (intrasystemic connections). To some extent, it may be seen as an inner basal ganglia regulator. Its mediator is GABA. The very fast spontaneous activity (contrary to that of medial pallidal neurons) is discontinuous with long intervals of silence "lasting up to several seconds or more" (DeLong, 1971). Some have low-frequency discharge. The responses to upstream stimulation of striatal neurons on pallidal (2 nuclei) in waking monkeys "consist of an initial inhibition at a mean latency of 14ms, followed by excitation, at a mean latency of 35ms" (Tremblay and Filion 1989). The excitation was essentially located close to the stimulation electrode and curtailed by excitation. "This arrangement suggests that excitation is used temporarily, to control the magnitude of the central striato-pallidal inhibitory signal and, spatially to focus and contrast it into a restricted number of pallidal neurons" (Tremblay and Filion 1989). This should be compared to morphological datas.
Lateral pallidal neurons are often multitargets and may correspond to several hodotypes (neuronal varieties according to the topology of their ways to their targets). From Sato et al. (2000), in macaques, the lateral pallidal neurons sends axons in the direction of the striatum only in 15.8%. The other lateral pallidal neurons (84,2%) project to three consecutive targets (medial pallidum, nigra reticulata and subthalamic nucleus) in 13,2% of the cases. The neurons projecting to the medial pallidum and subthalamic targets are 18,4%. Those projecting to the subthalamic nucleus and nigra reticulata 52,6%. The subthalamic nucleus is thus, in 84,2% of the cases, the target of lateral pallidal neurons. In return, the subthalamic nucleus, the privileged target of the lateral pallidum sends the majority of its axons to it (see below).
. The main group (90%) sends long axons directed posteriorly that, through collaterals, furnish several successive targets: the lateral region of the thalamus
(VO) (see human thalamus), the pars media of the central complex (see below), the pedunculopontine complex (Percheron et al., 1996) and to the retrorubral area (Parent and Parent (2004).
The major phylogenetic increase of the medial pallidum carries along that of a major output, the pallido-thalamic bundle, (successively the ansa
and fasciculus lenticularis, the comb system, Forel's fields H2, H and H1) and, above all, the appearance of a distinct nucleus in the lateral region of the thalamus, the nucleus ventralis oralis, VO (see thalamus
). The mediator is GABA
, forming the second segment of the inhibitory 2-path.
was first called the "tache noire" or "locus niger" (black spot) by Vicq d'Azyr (1786), then "substantia nigra" (Sömmering,1891) ('black substance', although it is not actually a substance). Only the melanin could be one, which would mean that the term only qualified the dopaminergic part (since only the dopaminergic neurons darken with age). The "nucleus substantiae nigrae" (Olszewski and Baxter 1954), the nigrum (the Vogts, 1941) or nigra in fact comprises two adjoining but contrasted components one of which is not black but pale. A fundamental distinction must be made between the dopaminergic ensemble (including the pars compacta) and the GABAergic ensemble continuing the pallidum in the other side of the capsule. The similarity of the neuronal type of the pallidum and that of the nigra was emphazised as soon as in 1896 by Mirto. The nigral neurons also are sparsely branched and long. The difference between pallidal and nigral neurons is only in the three-dimensional extension of their dendritic arborizations (François et al. 1987). The continuity of the bundle from the striatum to the pallidum and to the nigra (striato-pallidonigral bundle) was known. The particular synaptology is also the same. Nigral dendrites, as well as pallidal, but not as strictly, tend to be perpendicular to the arriving stiatal axons. However, in spite of so many solid arguments, it still appears today very difficult to convince scientific opinion to mentally extract the substantia nigra from the mesencephalon (where it is indeed located) and to place it fully in the basal ganglia system.
Another problem in the primate substantia nigra is that the pale part does not constitute a single entity. There are two subparts that belong to the basal ganglia core (i.e. receiving a dense projection from the striato-pallido-nigral bundle): the pars lateralis and the pars reticulata.
(Beckstead et al. 1981). "The monkey nigrotectal cells" ... (become) a spatially ... distinct subpopulation within the pars reticulata. Not all atlas trace a pars lateralis but others do , e.g., Riley, 1960 in man and Paxinos et al. ( 2000), in macaque.
The pars lateralis is the most lateral part of the substantia nigra
. It is frequently not considered separately from the pars reticulata. It is, however, on most of its dorsal border not covered by the substantia nigra
compacta. But its main difference with the pars reticulata is that it sends axons to the superior colliculus (Beckstead and Franckfurter, 1982, François et al. 1984). The border between the two basins is not clearcut but their difference in the participation of distincts subsystems is a sufficient reason for considering the two apart. The neurons that send axons to the superior colliculus have high discharge rates (80 to 100) (hence also a fastspiking pacemaker) and "the signal conveyed by the cells is a decrease in discharge rate" (Hikosaka and Wurtz, 1989). These neurons are involved in occular saccades that have taken a major interest in the last years.
or diffusa, is most often considered as a single entity with the pars lateralis. The term pars reticulata may thus describe either only the most medial part of the nigral ensemble, when a pars lateralis is retained, or the addition of the pars lateralis and reticulata. This must be carefully checked in papers. Due to major interspecific differences, the studied animal species must be verified. The name reticulata is simply an opposition to the dense pars compacta located above it. The border between the two is highly convoluted with deep fringes. Its neuronal genus is the same as that of the pallidum, with the same thick and long dendritic trees. It receives its synapses from the striatum in the same way as the pallidum. Striatonigral axons from the striosomes may form columns vertically oriented entering deeply in the pars reticulata (Lesvesque and Parent, 2005). The ventral dendrites of the pars compacta from the reverse direction go also deeply in it. The nigra also send axons to the pedunculo-pontine complex (Beckstead and Frankfurter, 1982) and to the parafascicular part of the central complex. The substantia nigra
reticulata is another "fast-spiking pacemaker" (Surmeier et al. 2005). Stimulations provoke no movements. Confirming anatomical data, few neurons respond to passive and active movements (there is no sensorimotor map) "but a large proportion shows responses that may be related to memory, attention or movement preparation" (Wicheman and Kliem, 2004) that would correspond to a more elaborate level than that of the medial pallidum. In addition to the massive striatopallidal connection, the nigra reticulata receives a dopamine innervation from the nigra compacta and glutamatergic axons from the pars parafascicularis of the central complex. It sends nigro-thalamic axons. There is no conspicuous nigro-thalamic bundle. Axons arrive medially to the pallidal afferences at the anterior and most medial part of the lateral region of the thalamus: the nucleus ventralis anterior (VA, differentiated from the VO receiving pallidal afferences, see Thalamus
).The mediator is GABA.
, striatal stimulations lead to a large convergence on pallidal neurons and a less precise mapping (Filion et al., 1988 and Tremblay et al. 1989) .
Focusing is not a property of the striatopallidal system. But, the very particular and contrasted geometry of the connection between striatal axons and pallidonigral dendrites offers particular conditions (the possibility for a very large number of combinations through local additions of simultaneous inputs to one tree or to several distant foci for instance). The disfocusing of the system is thought to be responsible for most of the parkinsonian series symptoms. The mechanism of focusing is not known yet. The structure of the dopaminergic innervation does not seem to allow it to operate for this function. More likely focusing is regulated by the upstream striatopallidal and corticostriatal systems.
The outmap of the nigra (lateralis reticulata) is less differentiated (Middleton and Strick, 2002).
is a part of the core of basal ganglia core since it directly receives synapses from striatal axons through the striatopallidonigral bundle. The long ventral dendrites of the pars compacta indeed plunge deep in the pars reticulata where they receive synapses from the bundle. However, its constitution, physiology and mediator contrast with the rest of the nigra. This explains why it is analysed here between the elements of the core and the regulators. Ageing leads to the blackening of its cell bodies, by deposit of melanin, visible by naked eye. This is the origin of the name of the ensemble, first "locus niger" (Vicq d'Azyr), meaning black place, and then "substantia nigra" (Sömmering), meaning black substance.
have larger and thicker dendritic arborizations than those of the pars reticulata
and lateralis.
The ventral dendrites descending in the pars reticulata receives inhibitory synapses from the initial axonal collaterals of pars reticulata neurons (Hajos and Greefield, 1994). Groups of dopaminergic neurons located more dorsally and posteriorly in the tegmentum are of the same type without forming true nuclei. The "cell groups A8 and A10" are spread inside the cerebral peduncule (François et al. 1999). They are not known to receive striatal afferences and are not in a topographical position to do so. The dopaminergic ensemble is thus also on this point inhomogeneous. This is another major difference with the pallidonigral ensemble. The axons of the dopaminergic neurons, that are thin and varicose, leave the nigra dorsally. They turn round the medial border of the subthalamic nucleus, enter the H2 field above the subthalamic nucleus, then cross the internal capsule to reach the upper part of the medial pallidum where they enter the pallidal laminae, from which they enter the striatum. They end intensively but inhomogeneously in the striatum
, rather in the matrix of the anterior part and rather in the striosomes dorsalwards. These authors insit on the extrastriatal dopaminergic innervation of other elements of the basal ganglia system: pallidum and subthalamic nucleus
.
neurons are "low-spiking pacemakers" (Surmeier et al. 2005), spiking at low frequency (0,2 to 10 Hz) (below 8, Schultz). The role of the dopaminergic neurons has been the source of a considerable literature. As the pathological disappearance of the black neurons was linked to the appearance of Parkinson's disease
(Tretiakoff
, 1919), their activity was thought to be "motor" . A major discovery has been that the stimulation of the black neurons had no motor effect. Their activity is in fact linked to reward
and prediction of reward. In a recent review (Schultz 2007), it is demonstrated that "phasic responses to reward-related events , notably reward-prediction errors, ...lead to ..dopamine release..." While it is thought that there could be different behavioral processes including long time regulation. Due to its widespread distribution, the dopaminergic system may regulate the basal ganglia
system in many places.
is located below the thalamus
; dorsally to the substantia nigra
and medial to the internal capsule
. The subthalamic nucleus is lenticular in form and of homogeneous aspect. It is made up of a particular neuronal species having rather long ellipsoid dendritic arborisations, devoid of spines, mimicking the shape of the whole nucleus (Yelnik and Percheron, 1979).The subthalamic neurons are "fast-spiking pacemakers" (Surmeier et al. 2005) spiking at 80 to 90 Hz. There are also about 7,5% of GABA microneurons participating in the local circuitry (Levesque and Parent 2005). The subthalamic nucleus receives its main afference from the lateral pallidum. Another afference comes from the cerebral cortex (glutamatergic), particularly from the motor cortex, which is too much neglected in models. A cortical excitation, via the subthalamic nucleus provokes an early short latency excitation leading to an inhibition in pallidal neurons (Nambu et al. 2000). Subthalamic axons leave the nucleus dorsally. Except for the connection to the striatum (17,3% in macaques), most of the principal neurons are multitargets and ffed axons to the other elements of the core of the basal ganglia (Sato et al. 2000). Some send axons to the substantia nigra medially and the medial and lateral nuclei of the pallidum laterally (3-target 21,3%). Some are 2-target with the lateral pallidum and the substantia nigra (2.7%) or the lateral pallidum and the medial(48%). Fewer are single target for the lateral pallidum. If one adds all those reaching this target, the main afference of the subthalamic nucleus is, in 82,7% of the cases, the lateral pallidum (external segment of the globus pallidus
. While striatopallidal and the pallido-subthalamic connections are inhibitory (GABA), the subthalamic nucleus utilises the excitatory neurotransmitter
glutamate.
Its lesion resulting in hemiballismus
is known for long. Chronic stereotactic stimulation of the nucleus suppress most of the symptoms of the Parkinson' syndrome, particularly dyskinesia induced by dopatherapy.
and lateral pallidum are both fast-firing pacemakers (Surmeier et al.2005). Together they constitute the "central pacemaker of the basal ganglia" (Plenz and Kitai,1999) with synchronous bursts. The pallido-subthalamic connection is inhibitory, the subthalamo-pallidal is excitatory. They are coupled regulators or coupled autonomous oscillators, the analysis of which has been insufficiently deepened. The lateral pallidum receives a lot of striatal axons, the subthalamic nucleus not. The subthalamic nucleus receives cortical axons, the pallidum not. The subsystem they make with their inputs and outputs corresponds to a classical systemic feedback circuit but it is evidently more complex.
s, 1941) or to the parafascicular nucleus (Niimi et al. 1960). This is undecidable. It has thus been proposed to group the three elements together in the regio Centralis (since it is a classical nucleus) and to name them from medially to laterally: n. centralis pars parafascicularis, pars media and pars paralateralis. The whole is parvalbumin rich. The first two medial parts are acetylcholinesterase rich. They are the source of the major, centralo-striatal, part of the thalamo-striatal connection, with glutamate as the mediator. The pars parafascicularis sends axons essentially to the associative striatum
. The pars media sends axons to the matrix compartment of the sensorimotor striatum through an important bundle (François et al. 1991).
In addition to cortical (see below), the pars parafascicularis receives afferences from the substantia nigra and the superior colliculus. The main afference of the pars media is the medial pallidum. The pars media is a part of the subcortical Nauta-Mehler's circuit (striatum-medial pallidum-pars media-striatum).
The pars paralateralis has essentially cortical relations particularly with the motor cortex. There are thus strong interconnections of the complex with the basal ganglia. The structure of the complex being different from that of the close intralaminar formation and having different connections, it has been proposed two decades ago to remove the central complex from the intralaminar elements and to link it to the basal ganglia system, where it may be classified among the regulators of the core.
Lesions of the complex have no known clinical effects. There are few physiological data in awake monkeys. For Matsumoto et al. (2001) the axons of the complex would supply striatal neurons with information about behaviorally significant sensory events. For Minamimoto and Kimura (2002) the region plays a role in attentional orienting to events occurring in the contralateral side.
. It is a part of the reticulate formation (Mesulam et al. 1989) having strong interrelations with the basal ganglia system. As indicated by its name, it is located at the junction between the pons and the cerebral peduncle, lateral to the decussation of the brachium conjunctivum. The complex is not homogeneous. An important part is made up of cholinergic (Ch5)(excitatory) neurons, which is also the case for the laterodorsal tegmental nucleus (Ch6) (Mesulam et al. 1989). Other neurons are GABAergic. The tracing of axons from the pedunculopontine complex has shown that they end intensively in the nigra reticulata first and to the compacta. Another strong innervation is observed in the subthalamic nucleus (Lavoie and Parent, 1994). Other targets are the pallidum (mainly medial) and the striatum. The complex receives direct afferences from the cortex and above all abundant direct afferences from the medial pallidum (Percheron et al. 1998) (inhibitory). It sends axons to the pallidal territory of the lateral region VO. The activity of the neurons is modified by movement, and precede it (Matsumura, Watanabe and Ohye (1997). All this led Mena-Segovia et al. (2004) to propose that the complex be linked in a way or another to the basal ganglia system. A review on its role in the system and in diseases is given by Pahapill and Lozano (2000). It plays an important role in awakeness and sleep. The complex must be left its double position and function. It is a part of the reticular formation. It is a regulator (regulating and being regulated) of the basal ganglia system.
, from the nigra lateralis. The two other major output subsystems are in the direction to the thalamus and from there to the cortex.
Starting from cercopidae, the ending from the two sources of the basal ganglia are located without mixture in front of the cerebellar territory (VIm or VL) (see thalamus
).
From there, there is also a complete separation of medial pallidal elements from nigral. Pallidal and nigral terminal arborisations do not mix (Percheron et al. 1998). The development of the medial pallidum creates the appearance of a new distinctive pallidal nucleus, the nucleus ventralis oralis VO, lateral to the nigral VA (Percheron, 2003). This distinction is of major importance (see thalamus).
indeed sends axons to the thalamic VImM, VA, Cpf, with links with the oculomotor cortex. In addition, through a thalamic relay, the nigra lateralis sends information to the premotor and also to the frontal cortex (Middleton and Strick, 2002).
and the fasciculus lenticularis, making in fact a single entity. The axons arrive at the medial face of the pallidum; from there, they cross the internal capsule where they form the comb system ("Kamm system" of Edinger, 1900). The axons arrives at the lateral border of the subthalamic nucleus. Passing above it they constitute the field H2 of Forel (1877). From there, they curve down towards the hypothalamus
. At field H, they turn abruptly. This has been the cause of historical mistakes as it was thought that the bundle had to pursue its ventral course. In fact the bundle goes up in a dorsolateral direction (forming the H1 field) and reach in this manner the ventral border of the thalamus. Pallidal axons have their own thalamic territory in the lateral region of the thalamus; everywhere separated from the cerebellar and from the nigral territories. The VO nucleus remains everywhere lateral in macaques and humans. It stained for calbindin
and acetylcholinesterase
. The axons ascend in the nucleus where they emit branches that widespreadly distribute "bunches" of axonal branches (Arrechi-Bouchhiouia et al.1996,1997). The distribution is such that if any somatotopical organisation exists, it may be only poor. The thalamocortical neurons of VO go preferentially to the supplementary motor cortex (SMA), to preSMA and to a lesser extent to the motor cortex. The pallidothalamic neurons also give branches to the pars media of the central complex (see above), which sends axons to the premotor and accessory motor cortex.
(ACC) and the oculomotor cortex (FEF and SEF), without significant connection to the motor cortex of the precentral gyrus. This set of thalamocortical outputs is different and distinct from that of the thalamic VO to which the medial pallidum connects.
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
form a major brain system in all species of vertebrates, but the basal ganglia of primates (including humans) have special features that justify a separate consideration. As in other vertebrates, the primate basal ganglia can be divided into striatal, pallidal, nigral, and subthalamic components. In primates, however, the two pallidal subdivisions are called the external and internal (or sometimes lateral and medial) segments of the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
, whereas in other species they are called the globus pallidus and entopeduncular nucleus. Also in primates, the striatum is divided by a large tract of white matter called the internal capsule
Internal capsule
The internal capsule is an area of white matter in the brain that separates the caudate nucleus and the thalamus from the lenticular nucleus. The internal capsule contains both ascending and descending axons....
into two masses of gray matter that early anatomists named the caudate nucleus
Caudate nucleus
The caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:...
and putamen
Putamen
The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...
-- in most other species no such division exists, and only the striatum as a whole is recognized. Beyond this, the complex topography of connections between the striatum and cortex means that functions are segregated within the primate striatum in ways that do not apply to other species.
A separate consideration of the primate basal ganglia is also warranted by the fact that different types of information are available than for other species. Large areas of the primate brain are devoted to vision; consequently the role of the basal ganglia in controlling eye movements has been studied almost exclusively in primates. Functional imaging
Functional imaging
Functional imaging , is a method of detecting or measuring changes in metabolism, blood flow, regional chemical composition, and absorption....
studies have been performed mainly using human subjects. Also, several major degenerative diseases of the basal ganglia, including Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
and Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
, are specific to humans, although "models" of them have been proposed for other species.
Corticostriatal connection
The whole system starts as a major output of the cerebral cortexCerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, about the same size as the corticopontine system opening the cerebellar system
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
. The corticostriatal connection represents a significant portion of the whole cortical output. Almost every part of the cortex, except for the primary olfactory, visual and auditory cortices, sends axons to the striatum. The origin of the connection is in the pyramidal neurons of layer V of the cortex. Corticostriate contributors, of the motor cortex at least, may be collaterals of axons descending lower in the nervous system. However, in primates, the majority of corticostriate axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s are monotarget, purely cortico-striate, thin and unbranched until they arrive in the striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
. The corticostriatal connection is glutamatergic and excitatory. This connection is not topologically as simple as was initially described by Kemp and Powell (1970), where the frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
projected anteriorly and the occipitotemporal lobes
Occipital lobe
The occipital lobe is the visual processing center of the mammalian brain containing most of the anatomical region of the visual cortex. The primary visual cortex is Brodmann area 17, commonly called V1...
posteriorly. Part of this distribution grossly remains, but the distribution is much more complex. One small cortical site can send terminal arborisations to several and distal striatal places. The cortico-striatal connection is the substrate of cortical information separation and recombination: axons from distinct cortical areas can systematically end together or separately. There is also a spatial reorganisation, a "remapping"(Flaherty and Graybiel, 1991).
The corticostriate connection is the first in a chain of strong reduction in numbers between emitter and receiver neurons, i.e. a numerical convergence. The effect of this is that if each striatocortical neuron has its own message, this will be mixed or compressed, leading to lesser definition of the input map.
Striatum
The striatumStriatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
is the main element of the basal ganglia system. It consists in a huge neuronal telencephalic
Telencephalon
The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
subcortical mass.
Neuronal constitution
In primates, the striatum has four neuronal genera: medium spiny neurons (96%), leptodendritic neurons (2%), spidery neurons (1%) and microneurons(1%). The dendriticDendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...
arborisations of the spiny neurons are spherical unless close to a border. Their overall dimensions depend on the animal species. Spines are of the same type as those of two other (telencephalic) acanthodendritic (acanthos means spine) genera, the pyramidal neurons of the cerebral cortex and the spiny neurons of the amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
. Most of these spines synapse with cortical afferents. The axons of spiny neurons have abundant and dense initial axonal collaterals acting fast on neighbouring neurons. The distal part is long and myelinated. The spiny neurons are GABAergic, constituting the first part of the inhibitory 2-path so particular to the system . The leptodendritic neurons (or Deiter's) stain for parvalbumin
Parvalbumin
Parvalbumin is a calcium-binding albumin protein with low molecular weight .It has three EF hand motifs and is structurally related to calmodulin and troponin C...
and have all the morphological properties of pallidal neurons. The spidery neurons are specific to primates. They have a big soma and short dendritic and axonal branches. They are the cholinergic
Cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...
neurons of the primate, with a morphology entirely different from that of non-primates. This must lead to great care in making physiopathological transfers. They are the "tonically active neurons" or TANs. The microneurons are local circuit neurons similar to those found in the thalamus for instance. They are GABAergic, and some may be dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
.
Physiology
The spontaneous activity of striatal neurons of awake monkeys is surprisingly "low or absent". Neurons are activated by cortical stimulation. At rest, spiny neurons are left in a state of low excitability by two types of potassium conductance that hyperpolarize the cell. Striatal neurons need strong synchronized input from their excitatory cortical afferences. In the sensorimotor striatum they respond to movements.Levels of organisation
There are several levels of organization of the striatum:- Gross anatomical subdivisions and territories
- The long oblique split of the striatum by the internal capsule creates the classic division into PutamenPutamenThe putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...
and CaudateCaudate nucleusThe caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:...
. The striatumStriatumThe striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
is a continuous mass. The gross anatomical division does not correspond exactly with the presently accepted anatomofunctional subdivision of the striatum in primates; relying on the differentiated territories of the corticostriatal axons. Endings of axons from the central region of the cortex, primary somatosensory, motor, premotor, accessory motor and anterior parietal, constitute a sensorimotor territory (or for short sensorimotor striatum) essentially putaminal, but does not cover the total extent of the putamen and slightly includes intracapsular fringes and the inferolateral border of the caudate. It is grossly somatotopically arranged with three oblique bands, one dorso-lateral related to the inferior limb, one intermediate to upper limb, and one medio-inferior to face. This is supposed an "associative" territory (the term is imperfect), located essentially in the caudate, above all orally and dorsally, which, however, does not cover the entire caudate volume. The separation between the two, sensorimotor and associative, territories may be in some places clearcut and observed using calbindin immunochemistry (the sensorimotor territory being negative). The isolation of a third ventral striatal part often qualified as "limbic" is more difficult. There is no general agreement on the position of its limit with the associative territory. Only one part is distinctive, the "nucleus accumbensNucleus accumbensThe nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
" (in fact a pars and not a nucleus) having the same morphological features as elsewhere but with particular immunostaining properties and, above all, a selectivity for the reception of axons from the subiculumSubiculumThe subiculum is the most inferior component of the hippocampal formation. It lies between the entorhinal cortex and the CA1 subfield of the hippocampus proper.-Paths:...
. A "shell" and a "core" are said to be also present in primates. They are however of small size relative to the other parts.
- Compartments
- Histochemistry has shown inhomogeneities with regards to the distribution of different molecules. The major compartment, the matrixMatrix (biology)In biology, matrix is the material between animal or plant cells, in which more specialized structures are embedded, and a specific part of the mitochondrion that is the site of oxidation of organic molecules. The internal structure of connective tissues is an extracellular matrix...
, as its name indicates, is considered as the basic element. It contains contrasting islands or striosomes that contain opiate receptors, D1 binding sites, and stain for acetylcholinesterase. This opposition, obvious in the head of the caudate, is not clear everywhere. Striosomes have no simple links with amygdalar afferents in primates. Striosomes rather represent the insular segregation of particular frontal axonal endings (posterior orbitofrontal/anterior insula and mediofrontal/anterior cingulate cortex). Matricial neurons are those contained in the matrix. Striosomal neurons are those contained in the striosome. They have been opposed as sources of distinctive efferents, which will be shown below.
Basal ganglia core
The basal gangliaBasal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
core includes the striatum and its direct targets, reached through the striato-pallidonigral bundle: the two nuclei of the pallidum and the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
.
Hodology to targets
There have been disputes concerning the origin of striatal axons projecting to different targets. In most parts of the neocortex, GABAergic neurons only send local connections, conversely inhibitory neurons in the striatum send long axons to their targets in the pallidum and the substantia nigra. Due to difficulties linked to the geometry of the system, the first data relying on tracing techniques led to the belief that there were specialised striato-pallidal or striato-nigral neurons each having histochemical particularities. A recent study in macaqueMacaque
The macaques constitute a genus of Old World monkeys of the subfamily Cercopithecinae. - Description :Aside from humans , the macaques are the most widespread primate genus, ranging from Japan to Afghanistan and, in the case of the barbary macaque, to North Africa...
s (following another one on the rat) has drastically changed the situation. Spiny neurons, generally, have several targets. This is not an archaic pattern since it is found in 90% of the cases in macaque monkeys versus 63,6% in the rat. Virtually all striatal axons have the lateral pallidum (the most voluminous) as their first target. 24/27 of the studied axons projected to the three consecutive targets, lateral pallidum, medial pallidum and nigra (lateralis and reticulata). There are no striatal axons projecting to the medial pallidum alone, to the nigra alone or only to both. Between matricial and striosomal axons, the only difference in axonal hodology
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
is that striosomal axons cross the whole lateral to medial extent of the nigra and emit (in macaques) 4 to 6 vertical collaterals, forming vertical columns entering deep inside the pars reticulata. The matricial neurons emit more sparsely branched axons. This general pattern of connectivity raises new problems. The main mediator of the striato- pallidonigral system is GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
, but with cotransmitters. The lateral pallidum stains for met-enkephalin
Met-enkephalin
[Met]enkephalin, sometimes referred to as opioid growth factor , is a naturally-occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. It is one of the two forms of enkephalin, the other being [leu]enkephalin...
, the medial for substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
and/or dynorphin
Dynorphin
Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 , multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin...
and the nigra for both. This likely means that a single axon is able to concentrate different comediators in different subtrees depending on the target. This considerably modifies several decades-old schemes and raises new questions.
Selectivity of striatal territories for targets
A study of the percentage of striatal axons from the sensorimotor and associative striatum distributed to targets found important differences. The lateral pallidum for instance receives mainly (68%) axons from the associative territory. On the reverse the medial pallidum is strongly sensorimotor (63%). The nigra is at first associative. This is confirmed by the effects of striatal stimulations.Constitution
The pallidonigral set comprises the direct targets of the striatal axons: the two nuclei of the pallidum and the pars lateralis and pars reticulata of the "substantia" nigra". One character of this ensemble is given by the very dense striato-pallidonigral bundle giving it its whitish aspect (pallidus means pale). In no ways has the pallidum the shape of a globe. After Foix and Nicolesco (1925) and some others, Cecile and Oskar Vogt (1941) suggested the term pallidum - also used by the Terminologia Anatomica (1998). They also proposed the term nigrum for replacing nigra, which is indeed not a substance; but this is generally not followed. The whole pallidonigral set is made up the same neuronal components. The majority is made up of very large neurons, poorly branched, strongly stained for parvalbumin, having very large dendritic arborisations (much larger in primates than in rodents) with straight and thick dendrites. Only the shape and direction of the dendritic arborizations differ between the pallidum and the nigra neurons. The pallidal dendritic arborisations are very large flat and discoidal. Their principal plane is parallel to the others and also parallel to the lateral border of the pallidum; thus perpendicular to the axis of the afferences. Since the pallidal discoidal discs are thin, they are crossed only for a short distance by striatal axons. On another hand, since they are wide, they are crossed by many striatalaxons from wide striatal parts. Since they are loose, the chances of contact are not very high. Striatal arborisations, in anotherhand, emit perpendicular branches participating in flat bands parallel to the lateral border, which increases the density of synapses in this direction. This is true for the striatal afferent but also for the subthalamic (see below).The synaptology of the set is uncommon and characteristic. The dendrites of the pallidal or nigral axons are entirely covered by synapses, without any apposition of glia. More than 90% of synapses are of striatal origin. One noticeable property of this ensemble is that not one of its elements receives cortical afferents.
Initial collaterals are present. However, in addition to the presence of various appendages at the distal extremity of the pallidal neurons that could act as elements of local circuitry, there are weak or no functional interrelations between pallidal neurons.
Lateral pallidum
The lateral pallidum is the lateral nucleus of the pallidum, the external "segment" of the globus pallidusGlobus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
(GPe). It is flat, curved and very extended (parasagittally and dorsoventrally). The three-dimensional shape of arborisations is discoid and flat. The arborisations are parallel to one another and to the lateral border of the pallidum. They are perpendicular to the striatal afferences. In addition to the striato-pallidal afference, the lateral pallidum receives a major connection from the subthalamic nucleus (see below). It also receives dopaminegic afferences from the nigra compacta.
Contrary to two other elements of the basal ganglia core, the lateral pallidum is not a source of output to the thalamus as it sends its axons essentially to other basal ganglia elements (intrasystemic connections). To some extent, it may be seen as an inner basal ganglia regulator. Its mediator is GABA. The very fast spontaneous activity (contrary to that of medial pallidal neurons) is discontinuous with long intervals of silence "lasting up to several seconds or more" (DeLong, 1971). Some have low-frequency discharge. The responses to upstream stimulation of striatal neurons on pallidal (2 nuclei) in waking monkeys "consist of an initial inhibition at a mean latency of 14ms, followed by excitation, at a mean latency of 35ms" (Tremblay and Filion 1989). The excitation was essentially located close to the stimulation electrode and curtailed by excitation. "This arrangement suggests that excitation is used temporarily, to control the magnitude of the central striato-pallidal inhibitory signal and, spatially to focus and contrast it into a restricted number of pallidal neurons" (Tremblay and Filion 1989). This should be compared to morphological datas.
Lateral pallidal neurons are often multitargets and may correspond to several hodotypes (neuronal varieties according to the topology of their ways to their targets). From Sato et al. (2000), in macaques, the lateral pallidal neurons sends axons in the direction of the striatum only in 15.8%. The other lateral pallidal neurons (84,2%) project to three consecutive targets (medial pallidum, nigra reticulata and subthalamic nucleus) in 13,2% of the cases. The neurons projecting to the medial pallidum and subthalamic targets are 18,4%. Those projecting to the subthalamic nucleus and nigra reticulata 52,6%. The subthalamic nucleus is thus, in 84,2% of the cases, the target of lateral pallidal neurons. In return, the subthalamic nucleus, the privileged target of the lateral pallidum sends the majority of its axons to it (see below).
Medial pallidum
The medial pallidum is the internal "segment" of the globus pallidus (GPi, Pallidum mediale), though absolutely similar to the lateral, is phylogenetically younger, as it appears only in primates. The entopeduncular nucleus of non-primate is not its equivalent. It does not have indeed a separate territory in the thalamus since its axons end together with nigral ones. In this respect the entopeduncular nucleus would rather be a lateral intracapsular extension of the nigra. The medial pallidum is separated into two parts (medial and lateral) by the lamina intermedia (with no known functional difference yet). As well as the lateral pallidum and the nigra lateralis and reticulata, see below), the medial pallidum is a "fast-spiking pacemaker" with spontaneous discharges in awake monkeys at about 90 Hz (Mink and Thach, 1991), 70 to 80 for Fillion and Tremblay (1991). In opposition to that of the lateral pallidum, the activity is continuous devoid of long intervals of silence (DeLong, 1971). In addition to the massive striatopallidal connection, the medial pallidum receives a dopaminergic innervation from the nigra compacta. Contrary to the lateral pallidum, it is one of the two major source of basal ganglia outputs. The first axonal component (10%) in macaque is in the direction of the habenulaHabenula
In neuroanatomy, habenula originally denoted the stalk of the pineal gland , but gradually came to refer to a neighboring group of nerve cells with which the pineal gland was believed to be associated, the habenular nucleus...
. The main group (90%) sends long axons directed posteriorly that, through collaterals, furnish several successive targets: the lateral region of the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
(VO) (see human thalamus), the pars media of the central complex (see below), the pedunculopontine complex (Percheron et al., 1996) and to the retrorubral area (Parent and Parent (2004).
The major phylogenetic increase of the medial pallidum carries along that of a major output, the pallido-thalamic bundle, (successively the ansa
Ansa lenticularis
The ansa lenticularis is a part of the brain, making up the superior layer of the substantia innominata of Meynert...
and fasciculus lenticularis, the comb system, Forel's fields H2, H and H1) and, above all, the appearance of a distinct nucleus in the lateral region of the thalamus, the nucleus ventralis oralis, VO (see thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
). The mediator is GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
, forming the second segment of the inhibitory 2-path.
Substantia nigra
The substantia nigraSubstantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
was first called the "tache noire" or "locus niger" (black spot) by Vicq d'Azyr (1786), then "substantia nigra" (Sömmering,1891) ('black substance', although it is not actually a substance). Only the melanin could be one, which would mean that the term only qualified the dopaminergic part (since only the dopaminergic neurons darken with age). The "nucleus substantiae nigrae" (Olszewski and Baxter 1954), the nigrum (the Vogts, 1941) or nigra in fact comprises two adjoining but contrasted components one of which is not black but pale. A fundamental distinction must be made between the dopaminergic ensemble (including the pars compacta) and the GABAergic ensemble continuing the pallidum in the other side of the capsule. The similarity of the neuronal type of the pallidum and that of the nigra was emphazised as soon as in 1896 by Mirto. The nigral neurons also are sparsely branched and long. The difference between pallidal and nigral neurons is only in the three-dimensional extension of their dendritic arborizations (François et al. 1987). The continuity of the bundle from the striatum to the pallidum and to the nigra (striato-pallidonigral bundle) was known. The particular synaptology is also the same. Nigral dendrites, as well as pallidal, but not as strictly, tend to be perpendicular to the arriving stiatal axons. However, in spite of so many solid arguments, it still appears today very difficult to convince scientific opinion to mentally extract the substantia nigra from the mesencephalon (where it is indeed located) and to place it fully in the basal ganglia system.
Another problem in the primate substantia nigra is that the pale part does not constitute a single entity. There are two subparts that belong to the basal ganglia core (i.e. receiving a dense projection from the striato-pallido-nigral bundle): the pars lateralis and the pars reticulata.
Nigra lateralis (SNl)
There are important interspecific differences in the organization of the substantia nigraSubstantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
(Beckstead et al. 1981). "The monkey nigrotectal cells" ... (become) a spatially ... distinct subpopulation within the pars reticulata. Not all atlas trace a pars lateralis but others do , e.g., Riley, 1960 in man and Paxinos et al. ( 2000), in macaque.
The pars lateralis is the most lateral part of the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
. It is frequently not considered separately from the pars reticulata. It is, however, on most of its dorsal border not covered by the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
compacta. But its main difference with the pars reticulata is that it sends axons to the superior colliculus (Beckstead and Franckfurter, 1982, François et al. 1984). The border between the two basins is not clearcut but their difference in the participation of distincts subsystems is a sufficient reason for considering the two apart. The neurons that send axons to the superior colliculus have high discharge rates (80 to 100) (hence also a fastspiking pacemaker) and "the signal conveyed by the cells is a decrease in discharge rate" (Hikosaka and Wurtz, 1989). These neurons are involved in occular saccades that have taken a major interest in the last years.
Nigra reticulata (SNr)
The pars reticulataPars reticulata
-Anatomy:Neurons in the pars reticulata are much less densely packed than those in the pars compacta . They are smaller and thinner than the dopaminergic neurons and conversely identical and morphologically similar to the pallidal neurons...
or diffusa, is most often considered as a single entity with the pars lateralis. The term pars reticulata may thus describe either only the most medial part of the nigral ensemble, when a pars lateralis is retained, or the addition of the pars lateralis and reticulata. This must be carefully checked in papers. Due to major interspecific differences, the studied animal species must be verified. The name reticulata is simply an opposition to the dense pars compacta located above it. The border between the two is highly convoluted with deep fringes. Its neuronal genus is the same as that of the pallidum, with the same thick and long dendritic trees. It receives its synapses from the striatum in the same way as the pallidum. Striatonigral axons from the striosomes may form columns vertically oriented entering deeply in the pars reticulata (Lesvesque and Parent, 2005). The ventral dendrites of the pars compacta from the reverse direction go also deeply in it. The nigra also send axons to the pedunculo-pontine complex (Beckstead and Frankfurter, 1982) and to the parafascicular part of the central complex. The substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
reticulata is another "fast-spiking pacemaker" (Surmeier et al. 2005). Stimulations provoke no movements. Confirming anatomical data, few neurons respond to passive and active movements (there is no sensorimotor map) "but a large proportion shows responses that may be related to memory, attention or movement preparation" (Wicheman and Kliem, 2004) that would correspond to a more elaborate level than that of the medial pallidum. In addition to the massive striatopallidal connection, the nigra reticulata receives a dopamine innervation from the nigra compacta and glutamatergic axons from the pars parafascicularis of the central complex. It sends nigro-thalamic axons. There is no conspicuous nigro-thalamic bundle. Axons arrive medially to the pallidal afferences at the anterior and most medial part of the lateral region of the thalamus: the nucleus ventralis anterior (VA, differentiated from the VO receiving pallidal afferences, see Thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
).The mediator is GABA.
Striato-pallidonigral connection
The striato-pallidonigral connection is a very particular one. It engages the totality of spiny striatal axons. Estimated numbers are 110 million in man, 40 in chimpanzees and 12 in macaques. The striato-pallido-nigral bundle is made up of thin, poorly myelinated axons from the striatal spiny neurons grouped into pencils "converging like the spokes of a wheel" (Papez, 1941). It gives its "pale" aspect to the receiving areas. The bundle strongly stains for iron using Perls technique (in addition to Fe it contains many heavy metals among which: Co, Cu, Mg, Pb ...).Convergence and focusing
After the huge reduction in number of neurons between the cortex and the striatum (see corticostriate connection), the striatopallido-nigral connection is a further reduction in the number of transmitting compared to receiving neurons. Numbers indicate that, for 31 million striatal spiny neurons in macaques, there are only lateral pallidal neurons,63000 medial pallidal, 18000 lateral nigral and 35000 in the pars reticulata. If the number of striatal neurons is divided by their total number, as an average, each target neuron may receive information from 117 striatal neurons. (Numbers in man lead to about the same ratio). A different approach starts from the mean surface of the pallidonigral target neurons and the number of synapses that they may receive. Each pallidonigral neuron may receive 70000 synapses. Each striatal neuron may contribute 680 synapses. This leads again to an approximation of 100 striatal neurons for one target neuron. This represents a huge, infrequent, reduction in neuronal connections. The consecutive compression of maps cannot preserve finely distributed maps (as in the case for instance of sensory systems). The fact that a strong anatomical possibility of convergence exists does not means that this is constantly used. A recent modeling study starting from entirely 3-d reconstructed pallidal neurons showed that their morphology alone is able to create a center-surround pattern of activity (Mouchet and Yelnik, 2004). Physiological analyses have shown a central inhibition/peripheral excitation pattern (Tremblay and Filion, 1989), able of focusing the pallidal response in normal conditions. Percheron and Filion (1991) thus argued for a "dynamically focused convergence". Disease, is able to alter the normal focusing. In monkeys intoxicated by MPTPMPTP
MPTP is a neurotoxin precursor to MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain...
, striatal stimulations lead to a large convergence on pallidal neurons and a less precise mapping (Filion et al., 1988 and Tremblay et al. 1989) .
Focusing is not a property of the striatopallidal system. But, the very particular and contrasted geometry of the connection between striatal axons and pallidonigral dendrites offers particular conditions (the possibility for a very large number of combinations through local additions of simultaneous inputs to one tree or to several distant foci for instance). The disfocusing of the system is thought to be responsible for most of the parkinsonian series symptoms. The mechanism of focusing is not known yet. The structure of the dopaminergic innervation does not seem to allow it to operate for this function. More likely focusing is regulated by the upstream striatopallidal and corticostriatal systems.
Synaptology and combinatory
The synaptology of the striato- pallidonigral connection is so peculiar as to be recognized easily. Pallidonigral dendrites are entirely covered with synapses without any apposition of glia (Fox et al.,1974, Di Figlia et al. 1982). This gives in sections characteristic images of "pallissades" or of "rosettes". More than 90% of these synapses are of striatal origin. The few other synapses such as the dopaminergic or the cholinergic are interspersed among the GABAergic striatonigral synapses. The way striatal axons distribute their synapses is a disputed point. The fact that striatal axons are seen parallel to dendrites as "woolly fibers" has led to exaggerate the distances along which dendrites and axons are parallel. Striatal axons may in fact simply cross the dendrite and give a single synapse. More frequently the striatal axon curves its course and follow the dendrite forming "parallel contacts" for a rather short distance. The average length of parallel contacts was found to be 55 micrometres with 3 to 10 boutons (synapses). In another type of axonal pattern the afferent axon bifurcates and gives two or more branches, parallel to the dendrite, thus increasing the number of synapses given by one striatal axon. The same axon may reach other parts of the same dendritic arborisation (forming "random cascades") With this pattern, it is more than likely that 1 or even 5 striatal axons are not able to influence (to inhibit) the activity of one pallidal neuron. Certain spatio-temporal conditions would be necessary for this, implying more afferent axons.Pallidonigral outmaps
What is described above concerned the input map or "inmap" (corresponding to the spatial distribution of the afferent axons from one source to one target). This does not correspond necessarily to the output map or outmap (corresponding to the distribution of the neurons in relation to their axonal targets). Physiological studies and transsynaptic viral markers have shown that islands of pallidal neurons (only their cell bodies or somata, or trigger points) sending their axons through their particular thalamic territories (or nuclei) to one determined cortical target are organized into radial bands (Hoover and Strick 1994 and Middleton and Strick, 1994). These were assested to be totally representative of the pallidal organisation. This is certainly not the case. Pallidum is precisely one cerebral place where there is a dramatic change between one afferent geometry and a completely different efferent one. The inmap and the outmap are totally different. This is an indication of the fundamental role of the pallidonigral set: the spatial reorganisation of information for a particular "function" , which is predictably a particular reorganisation within the thalamus preparing a distribution to the cortex.The outmap of the nigra (lateralis reticulata) is less differentiated (Middleton and Strick, 2002).
Substantia nigra compacta (SNc) and nearby dopaminergic elements
In strict sense, the pars compactaPars compacta
-Anatomy:In humans, the nerve cell bodies of the pars compacta are coloured black by the pigment neuromelanin. The degree of pigmentation increases with age. This pigmentation is visible as a distinctive black stripe in brain sections and is the origin of the name given to this area. The neurons...
is a part of the core of basal ganglia core since it directly receives synapses from striatal axons through the striatopallidonigral bundle. The long ventral dendrites of the pars compacta indeed plunge deep in the pars reticulata where they receive synapses from the bundle. However, its constitution, physiology and mediator contrast with the rest of the nigra. This explains why it is analysed here between the elements of the core and the regulators. Ageing leads to the blackening of its cell bodies, by deposit of melanin, visible by naked eye. This is the origin of the name of the ensemble, first "locus niger" (Vicq d'Azyr), meaning black place, and then "substantia nigra" (Sömmering), meaning black substance.
Structure
The densely distributed neurons of the pars compactaPars compacta
-Anatomy:In humans, the nerve cell bodies of the pars compacta are coloured black by the pigment neuromelanin. The degree of pigmentation increases with age. This pigmentation is visible as a distinctive black stripe in brain sections and is the origin of the name given to this area. The neurons...
have larger and thicker dendritic arborizations than those of the pars reticulata
Pars reticulata
-Anatomy:Neurons in the pars reticulata are much less densely packed than those in the pars compacta . They are smaller and thinner than the dopaminergic neurons and conversely identical and morphologically similar to the pallidal neurons...
and lateralis.
The ventral dendrites descending in the pars reticulata receives inhibitory synapses from the initial axonal collaterals of pars reticulata neurons (Hajos and Greefield, 1994). Groups of dopaminergic neurons located more dorsally and posteriorly in the tegmentum are of the same type without forming true nuclei. The "cell groups A8 and A10" are spread inside the cerebral peduncule (François et al. 1999). They are not known to receive striatal afferences and are not in a topographical position to do so. The dopaminergic ensemble is thus also on this point inhomogeneous. This is another major difference with the pallidonigral ensemble. The axons of the dopaminergic neurons, that are thin and varicose, leave the nigra dorsally. They turn round the medial border of the subthalamic nucleus, enter the H2 field above the subthalamic nucleus, then cross the internal capsule to reach the upper part of the medial pallidum where they enter the pallidal laminae, from which they enter the striatum. They end intensively but inhomogeneously in the striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
, rather in the matrix of the anterior part and rather in the striosomes dorsalwards. These authors insit on the extrastriatal dopaminergic innervation of other elements of the basal ganglia system: pallidum and subthalamic nucleus
Subthalamic nucleus
The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
.
Physiology
Contrarily to the neurons of the pars reticulata-lateralis, dopaminergicDopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neurons are "low-spiking pacemakers" (Surmeier et al. 2005), spiking at low frequency (0,2 to 10 Hz) (below 8, Schultz). The role of the dopaminergic neurons has been the source of a considerable literature. As the pathological disappearance of the black neurons was linked to the appearance of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
(Tretiakoff
Konstantin Tretiakoff
Konstantin Nikolaevitch Tretiakoff was a Russian neuropathologist. He was born in Fergana, Uzbekistan, as a son of military physician, who was member of Pierre Bonvalot's first Pamir expedition. He studied medicine in L'Assistance Publique des Hopitaux de Paris. He received his doctorate in 1919...
, 1919), their activity was thought to be "motor" . A major discovery has been that the stimulation of the black neurons had no motor effect. Their activity is in fact linked to reward
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
and prediction of reward. In a recent review (Schultz 2007), it is demonstrated that "phasic responses to reward-related events , notably reward-prediction errors, ...lead to ..dopamine release..." While it is thought that there could be different behavioral processes including long time regulation. Due to its widespread distribution, the dopaminergic system may regulate the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
system in many places.
Subthalamic nucleus, or corpus Lyuisi
As indicated by its name, the subthalamic nucleusSubthalamic nucleus
The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
is located below the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
; dorsally to the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
and medial to the internal capsule
Internal capsule
The internal capsule is an area of white matter in the brain that separates the caudate nucleus and the thalamus from the lenticular nucleus. The internal capsule contains both ascending and descending axons....
. The subthalamic nucleus is lenticular in form and of homogeneous aspect. It is made up of a particular neuronal species having rather long ellipsoid dendritic arborisations, devoid of spines, mimicking the shape of the whole nucleus (Yelnik and Percheron, 1979).The subthalamic neurons are "fast-spiking pacemakers" (Surmeier et al. 2005) spiking at 80 to 90 Hz. There are also about 7,5% of GABA microneurons participating in the local circuitry (Levesque and Parent 2005). The subthalamic nucleus receives its main afference from the lateral pallidum. Another afference comes from the cerebral cortex (glutamatergic), particularly from the motor cortex, which is too much neglected in models. A cortical excitation, via the subthalamic nucleus provokes an early short latency excitation leading to an inhibition in pallidal neurons (Nambu et al. 2000). Subthalamic axons leave the nucleus dorsally. Except for the connection to the striatum (17,3% in macaques), most of the principal neurons are multitargets and ffed axons to the other elements of the core of the basal ganglia (Sato et al. 2000). Some send axons to the substantia nigra medially and the medial and lateral nuclei of the pallidum laterally (3-target 21,3%). Some are 2-target with the lateral pallidum and the substantia nigra (2.7%) or the lateral pallidum and the medial(48%). Fewer are single target for the lateral pallidum. If one adds all those reaching this target, the main afference of the subthalamic nucleus is, in 82,7% of the cases, the lateral pallidum (external segment of the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
. While striatopallidal and the pallido-subthalamic connections are inhibitory (GABA), the subthalamic nucleus utilises the excitatory neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
glutamate.
Its lesion resulting in hemiballismus
Hemiballismus
Hemiballismus is a very rare movement disorder. It is 500 times rarer than Parkinson's disease. Its effects can sometimes be severe enough to prevent patients from being able to perform daily functions. It is usually associated with structural brain lesions but can occur with metabolic abnormalities...
is known for long. Chronic stereotactic stimulation of the nucleus suppress most of the symptoms of the Parkinson' syndrome, particularly dyskinesia induced by dopatherapy.
Subthalamo-lateropallidal pacemaker
As said before, the lateral pallidum has purely intrinsic basal ganglia targets. It is particularly linked to the subthalamic nucleus by two-way connections. Contrary to the two output sources (medial pallidum and nigra reticulata), neither the lateral pallidum or the subthalmic nucleus send axons to the thalamus. The subthalamic nucleusSubthalamic nucleus
The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
and lateral pallidum are both fast-firing pacemakers (Surmeier et al.2005). Together they constitute the "central pacemaker of the basal ganglia" (Plenz and Kitai,1999) with synchronous bursts. The pallido-subthalamic connection is inhibitory, the subthalamo-pallidal is excitatory. They are coupled regulators or coupled autonomous oscillators, the analysis of which has been insufficiently deepened. The lateral pallidum receives a lot of striatal axons, the subthalamic nucleus not. The subthalamic nucleus receives cortical axons, the pallidum not. The subsystem they make with their inputs and outputs corresponds to a classical systemic feedback circuit but it is evidently more complex.
Central region of the thalamus (C)
The central complex is the so-called centre-médian- parafascicular complex. Contrary to the current claim it does not topographically, histologically or functionally belong to the intralaminar group. Located at the inferior part of the thalamus, it is almost everywhere surrounded by a capsule making it a closed region. In upper primates, starting from the cercopithecidae, it is made up not of two but of three parts with their own neuronal species (Fenelon et al. 1994). From there, two opposed interpretations were proposed concerning the belonging of the intermediate part: either to the centre médian (the VogtVogt
A Vogt ; plural Vögte; Dutch voogd; Danish foged; ; ultimately from Latin [ad]vocatus) in the Holy Roman Empire was the German title of a reeve or advocate, an overlord exerting guardianship or military protection as well as secular justice...
s, 1941) or to the parafascicular nucleus (Niimi et al. 1960). This is undecidable. It has thus been proposed to group the three elements together in the regio Centralis (since it is a classical nucleus) and to name them from medially to laterally: n. centralis pars parafascicularis, pars media and pars paralateralis. The whole is parvalbumin rich. The first two medial parts are acetylcholinesterase rich. They are the source of the major, centralo-striatal, part of the thalamo-striatal connection, with glutamate as the mediator. The pars parafascicularis sends axons essentially to the associative striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
. The pars media sends axons to the matrix compartment of the sensorimotor striatum through an important bundle (François et al. 1991).
In addition to cortical (see below), the pars parafascicularis receives afferences from the substantia nigra and the superior colliculus. The main afference of the pars media is the medial pallidum. The pars media is a part of the subcortical Nauta-Mehler's circuit (striatum-medial pallidum-pars media-striatum).
The pars paralateralis has essentially cortical relations particularly with the motor cortex. There are thus strong interconnections of the complex with the basal ganglia. The structure of the complex being different from that of the close intralaminar formation and having different connections, it has been proposed two decades ago to remove the central complex from the intralaminar elements and to link it to the basal ganglia system, where it may be classified among the regulators of the core.
Lesions of the complex have no known clinical effects. There are few physiological data in awake monkeys. For Matsumoto et al. (2001) the axons of the complex would supply striatal neurons with information about behaviorally significant sensory events. For Minamimoto and Kimura (2002) the region plays a role in attentional orienting to events occurring in the contralateral side.
Pedunculopontine complex
The pedunculopontine complex (nucleus tegmenti pedunculopontinus, Olszewski and Baxter 1954) is not a primary part of the basal gangliaBasal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
. It is a part of the reticulate formation (Mesulam et al. 1989) having strong interrelations with the basal ganglia system. As indicated by its name, it is located at the junction between the pons and the cerebral peduncle, lateral to the decussation of the brachium conjunctivum. The complex is not homogeneous. An important part is made up of cholinergic (Ch5)(excitatory) neurons, which is also the case for the laterodorsal tegmental nucleus (Ch6) (Mesulam et al. 1989). Other neurons are GABAergic. The tracing of axons from the pedunculopontine complex has shown that they end intensively in the nigra reticulata first and to the compacta. Another strong innervation is observed in the subthalamic nucleus (Lavoie and Parent, 1994). Other targets are the pallidum (mainly medial) and the striatum. The complex receives direct afferences from the cortex and above all abundant direct afferences from the medial pallidum (Percheron et al. 1998) (inhibitory). It sends axons to the pallidal territory of the lateral region VO. The activity of the neurons is modified by movement, and precede it (Matsumura, Watanabe and Ohye (1997). All this led Mena-Segovia et al. (2004) to propose that the complex be linked in a way or another to the basal ganglia system. A review on its role in the system and in diseases is given by Pahapill and Lozano (2000). It plays an important role in awakeness and sleep. The complex must be left its double position and function. It is a part of the reticular formation. It is a regulator (regulating and being regulated) of the basal ganglia system.
Outputs of the basal ganglia system
Many connections of the basal ganglia are between elements of the basal ganglia. There are few output external targets. One is the superior colliculusSuperior colliculus
The optic tectum or simply tectum is a paired structure that forms a major component of the vertebrate midbrain. In mammals this structure is more commonly called the superior colliculus , but, even in mammals, the adjective tectal is commonly used. The tectum is a layered structure, with a...
, from the nigra lateralis. The two other major output subsystems are in the direction to the thalamus and from there to the cortex.
Starting from cercopidae, the ending from the two sources of the basal ganglia are located without mixture in front of the cerebellar territory (VIm or VL) (see thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
).
From there, there is also a complete separation of medial pallidal elements from nigral. Pallidal and nigral terminal arborisations do not mix (Percheron et al. 1998). The development of the medial pallidum creates the appearance of a new distinctive pallidal nucleus, the nucleus ventralis oralis VO, lateral to the nigral VA (Percheron, 2003). This distinction is of major importance (see thalamus).
Nigra lateralis to superior colliculus
The nigra lateralis made up of the same cell type than the pars reticulata differs by its targets. The now well established connection to the tectum in macaques (Jayaraman et al.1977, François et al.1984) is not given its full value. The superior colliculusSuperior colliculus
The optic tectum or simply tectum is a paired structure that forms a major component of the vertebrate midbrain. In mammals this structure is more commonly called the superior colliculus , but, even in mammals, the adjective tectal is commonly used. The tectum is a layered structure, with a...
indeed sends axons to the thalamic VImM, VA, Cpf, with links with the oculomotor cortex. In addition, through a thalamic relay, the nigra lateralis sends information to the premotor and also to the frontal cortex (Middleton and Strick, 2002).
Medial pallidum to thalamic VO and from there to cortex
Axons from the pallidum to the thalamus form the ansa lenticularisAnsa lenticularis
The ansa lenticularis is a part of the brain, making up the superior layer of the substantia innominata of Meynert...
and the fasciculus lenticularis, making in fact a single entity. The axons arrive at the medial face of the pallidum; from there, they cross the internal capsule where they form the comb system ("Kamm system" of Edinger, 1900). The axons arrives at the lateral border of the subthalamic nucleus. Passing above it they constitute the field H2 of Forel (1877). From there, they curve down towards the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. At field H, they turn abruptly. This has been the cause of historical mistakes as it was thought that the bundle had to pursue its ventral course. In fact the bundle goes up in a dorsolateral direction (forming the H1 field) and reach in this manner the ventral border of the thalamus. Pallidal axons have their own thalamic territory in the lateral region of the thalamus; everywhere separated from the cerebellar and from the nigral territories. The VO nucleus remains everywhere lateral in macaques and humans. It stained for calbindin
Calbindin
Calbindin refers to several calcium-binding proteins. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals...
and acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
. The axons ascend in the nucleus where they emit branches that widespreadly distribute "bunches" of axonal branches (Arrechi-Bouchhiouia et al.1996,1997). The distribution is such that if any somatotopical organisation exists, it may be only poor. The thalamocortical neurons of VO go preferentially to the supplementary motor cortex (SMA), to preSMA and to a lesser extent to the motor cortex. The pallidothalamic neurons also give branches to the pars media of the central complex (see above), which sends axons to the premotor and accessory motor cortex.
Nigra reticulata to thalamic VA and from there to cortex
Nigral axons go up dorsally without forming a clear distinctive bundle. They reach the inferomedial border of the thalamus. The nigral target thalamic territory (VA) is medial to the pallidal (VO). It is crossed by the mammillothalamic bundle. In the monkey, the nucleus is usually divided into a magnocellular part, medial and close to the mammillothalamic bundle, and a mediocellular part. In the human brain, the majority of the nucleus is composed of the magnocellular component. In any case, in macaques, the afferences from the nigra do not care about these cytoarchitectonic subdivisions. In addition to the nigral afference, VA receives axons from the tectum (superior colliculus) and from the amygdala (basal complex), which makes a singular set of afferences. Thalamocortical projections from VA travel to their own distinctive cortical territory made up of the frontal (premotor), the anterior cingulate cortexAnterior cingulate cortex
The anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain...
(ACC) and the oculomotor cortex (FEF and SEF), without significant connection to the motor cortex of the precentral gyrus. This set of thalamocortical outputs is different and distinct from that of the thalamic VO to which the medial pallidum connects.
Sources
- Albin, R.L., Young, A.B., Penney. J.B. (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci. 12: 366-375
- Alexander, G.E., Crutcher, M.D. DeLong, M.R (1990)Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, prefrontal and limbic functions. In Uylings, H.B.M. et al. (eds) Prog. Brain Res. Vol.85 pp. 119–146
- Arecchi-Bouchhioua P, Yelnik J, Francois C, Percheron G, Tande D.(1996) 3-D tracing of biocytin-labelled pallido-thalamic axons in the monkey. Neuroreport.7:981-984.id=PMID
- Arrechi-Bouchhioua, P., Yelnik, J., Percheron, G., Tande, D. (1997) Three dimensional morphology and distribution of pallidal axons projecting to both the lateral region of the thalamus and the central complex in primate. Brain Res. 754:311-314 id=PMID
- Bar-Gad, I, Heimer, G., Ritov, Y, Bergman, H. (2003) Functional correlations between neighbouring neurons in the primate globus pallidus are weak or non existent. J. Neurosci.23:4012-4016 id=PIMD
- Bar-Gad, I, Morris, G., Bergman, H. (2003) Information processing, dimensionality, reduction and reinforcement in the basal ganglia. Progr. Neurobiol.71:439-477
- Beckstead, R.M. and Frankfurter, A. (1982) The distribution and some morphological features of substantia nigra neurons that project to the thalamus , superior colliculus and pedunculopontine nucleus in monkey. Neuroscience.7: PMID
- Beckstead, R.M., Edwards, S.B. and Frankfurter, A. (1981) A comparison of the intranigral distribution of nigrotectal neurons labeled with horseradish peroxidase in the monkey, cat and rat. J. Neurosci. 1: 121-125 PMID
- Brauer, K, Haüsser, M., Härtig, W. and Arendt, T. (2000) The shell-core dichotomy of nucleus accumbens in the rhesus monkey as revealed by double-immunofluorescence and morphology of cholinergic interneurons. Brain Res. 858: 151-162
- Chan, C.S., Shigemoto, R., Mercer, J.N., Surmeier, D.J. (2002) HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. J. Neurosci. 24:
- Cossette, M., Lecomte, F., Parent, A. (2005) Morphology and distribution of dopaminergic intrinsic to the human striatum. J.Chem. Neuroanat.,29: 1-11
- Czubayko, U. and Plenz, D. (2002) Fast synaptic transmission between striatal spiny projecting neurons. Proc. Nat. Acad. Sci.99:15764-15769
- DeLong, M.R. (1971) Activity of the pallidum during movement. J. Neurophysiol. 34:417-424
- DeLong, M.R. and Georgopoulos, A.P. (1980) Motor function of the basal ganglia. In Handbook of Physiology. I-Nervous system. Vol. II Motor control. Part 2. Ch.21. pp. 1017–1061
- diFiglia, M., Pasik, P., Pasik, T. (1982) A Golgi and ultrastructural study of the monkey globus pallidus. J. Comp. Neurol. 212:53-75
- Eblen, F, Graybiel;, A.M. (1995) Highly restricted origin of prefrontal cortical inputs to striosomes in monkeys. J. Neurosci.15:5999-6013 id=PIMB
- Fenelon, G., Percheron, G., Parent, A., Sadikot, Fenelon, G., Yelnik, J. (1991) Topography of the projection of the central complex of the thalamus to the sensorimotor striatal territory in monkeys. J. Comp. Neurol. 305: 17-34 id=PIMB
- Fenelon, G. Yelnik, J., François, C. Percheron, G. (1994) Central complex of the thalamus: a quantitative analysis of neuronal morphology. J. Comp. Neurol. 342: 463-479 id=PIMB
- Filion, M.,Tremblay, L., Bédard, P.J (1988) Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkinsonian monkeys. Brain Res. 444: 165-176
- Filion, M. and Tremblay, L. (1991) Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res.547:142-151
- Flaherty, A.W and Graybiel, A.M. (1991) Corticostriatal transformations in the primate somatosensory system . Projections from physiologically mapped body-part representations. J. Neurosci.66:1249-1263
- Fox C.A, Andrade A.N, Lu Qui I.J, Rafols J.A.(1974) The primate globus pallidus: a Golgi and electron microscopic study. J Hirnforsch.15:75-93.id=PMID
- Francois C, Percheron G, Yelnik J.(1984) Localization of nigrostriatal, nigrothalamic and nigrotectal neurons in ventricular coordinates in macaques. Neuroscience.13:61-76.id=PMID
- François, C., Percheron, G., Parent, A., Sadikot, Fenelon, G., Yelnik, J (1991) Topography of the projection from the central complex of the thalamus to the sensorimotor striatal territory in monkey. J. Comp. Neurol. 305:17-34
- François, C., Tande, D., Yelnik, J., Hirsh, E.C. (2002) Distribution and morphology of nigral axons projecting to the thalamus in primates. J.Comp. Neurol. 447:249-260 id=PMID.
- François, C., Yelnik, J.,Percheron, G. (1996) A stereotactic atlas of the basal ganglia in Macaques. Brain Res. Bull. 41: 151-158
- François, C., Yelnik, J.,Percheron, G.and Tandé, D.(1994) Calbindin-D-28K as a marker of the associative coertical territory of the striatum of macaques. Brain Res. 633: 331-336
- Goldman, P.S. and Nauta, W.J. (1977) An intricately patterned prefronto-caudate projection in the rhesus monkey. J. Comp. Neurol. 72:369-386 id=PIMB401836
- Haber, S. and Elde, R. (1981) Correlation between Met-enkephalin and sustance P immunoreactivity in the primate globus pallidus. Neurosci. 6:1291-1297
- Hajos, M and Greenfield, S.A. (1994) Synaptic connections between pars compacta and pars reticulata neurons: electophysiological evidence for functional modules within the substantia nigra. Brain Res. 660: 216-224.
- Hikosaka, O. and Wurtz, R.H. (1989) The basal ganglia. in Wurtz and Goldberg (eds) The neurobiology of saccadic eye movements. Elsevier. Amsterdam.pp. 257–281
- Hoover, J.E. and Strick, P.L. (1993) Multiple output channels in the basal ganglia. Science. 259: 819-821
- Jarayaman, A. and Carpenter, M.B. (1977) Nigrotectal projection in the monkey: an autoradiographic study. Brain Res. 135: 147-152 id=PMID410480
- Jenkinson, N., Nandi, D., Oram, R., Stein, J.F., Aziz, T.Z. (2006) Pedunculopontine nucleus electric stimulation alleviates akinesia independently of dopaminergic mechanisms. Neuroreport 17:639-641
- Kemp, J.M. and Powell, T.P.S. (1970) The cortico-striate connection in the monkey. Brain, 93: 525-546
- Kimura, M., Yamada, H. and Matsumoto (2003) Tonically active neurons in the striatum encode motivational contexts of actions. Brain and develop.25: S20-S23 id=PMID
- Kitano, H., Tanibuchi, I. and Jinnai, K. (1998) The distribution of neurons in the substantia nigra pars reticulata with input from the motor, premotor and prefrontal areas of the cerebral cortex in monkeys. Brain Res. 784:228-238
- Künzle, H. (1975) Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia. an autoradiographic studyin Macaca fascicularis. Brain. Res. 88:195-209 id=PMID 50112
- Lavoie, B. and Parent, A. (1994) Pedunculopontine nucleus in the squirrel monkey: projection to the basal ganglia as revealed by anterograde track tracing. J. Comp. Neurol.
- Levesque, M., Bédard, A., Cossette, M., Parent, A. (2003) Novel aspets of the chemical anatomy of the striatum and its efferent projections. Chem. Neuroanat. 26: 271-281
- Levesque, M. and Parent, A. (2005) The striatofugal fiber system in primates: a reevaluation of its organization based on single-axon tracing studies. PNAS.102:
- Levesque, J.C. and Parent, A. (2005) GABAergic interneurons in human subthalamic nucleus. Mov. Disord. 20:574-584
- Matsumoto, N., Minamimoto, T, Graybiel, A.M, Kimura, M. (2001) Neurons in the thalmic CM-Pf complex supply striatal neurons with information about behaviorally significant sensory events. J. Neurophysiol. 85: 960-976
- Matsumura, M., Watanabe, K. and Ohye, C. (1997) Single-unit activity in the primate nucleus tegmenti pedunculopontinus related to voluntary arm movement. Neurosci. Res.28: 155-165.
- Mesulam, M-M, Geula, C., Bothwell, M.A.,Hersh, C.B.(1989) Human reticular formation: cholinergic neurons of the pedunculopontine and the lateral dorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons. J. Comp. Neurol. 22:611-631
- Middleton, F.A and Strick, P.L (1994) anatomical evidence for cerebellar and basal ganglia involvvement in higher cognitive function. Science. 266: 458-461
- Middleton, F.A and Strick, P.L (2002) Basal ganglia "projections" to the prefrontal cortex of the primate. Cereb. Cortex.12: 926-935
- Minamumoto, T., Kimura, M. (2002) Participation of the thalamic CM-Pf complex in attentional orienting. J. Neurophysiol. 87:
- Mink, J.W., and Thach, W.T. (1991) Basal ganglia motor control .I. Non exclusive relation of pallidal discharge in five movement modes. J. Neurophysiol. 65: 273-300
- Mirto, D. (1896) Contributione alla fina anatomia della substantia nigra di Soemering e del pedunculo cerebrale dell'uomo. Riv. Sper. Fren. Med. leg. 22:197-210
- Mouchet, P. and Yelnik, J. (2004) Basic electronic properties of primate pallidal neurons as inferred from a detailed analysis of their morphology: a modeling study. Synapse 54: 11-23
- Munro-Davies, L.E., Winter, J., Aziz, T.Z., Stein, J.F (1999) The role of the pedunculopontine region in basal-ganglia mechanisms of akinesia. Exp. Brain Res. 129: 511-517
- Nambu, A., Tokuno, H, Hamada, I, Kita, H., Himanishi, M. , Akazawa, T. Ikeuchi, Y, Hasegawa, N. (2000) Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in monkey. J. Neurophysiol. 84: 289-300 id=PMID
- Niimi, K., Katayama, K., Kanaseki, T., Morimoto, K. (1960) Studies on the derivation of the centre median of Luys. Tokushima J. Exp. Med. 2: 261-268
- Olszewski, J. and Baxter, D. (1954, 2d ed 1982) Cytoarchitecture of the human brain stem. Karger. Basel.
- Pahapill, P.A. and Lozano, A. M. (2000) The pedunculopontine nucleus and Parkinson's disease. Brain, 123:1767-1783
- Parent, M. and Parent, M. (2004) The pallidofugal motor fiber system in primates. Park. Relat. Disord. 10: 203-211
- Parent, M. and Parent, M. (2005) Single-axon tracing and three dimensional reconstruction of centre median-parafascicular thalamic neurons in primates. J. Comp. Neurol.
- Parent, M. and Parent, M. (2006) Single-axon tracing study of corticostriatal projections arising from primary motor cortex in primates. J. Comp. Neuro.496: 202-213 PMID
- Paxinos, G., Huang, X.F. and Toga, A.W. (2000) The rhesus monkey brain. Academic Press. San Diego
- Percheron, G. (1991) The spatial organization of information processing in the striato-pallido-nigral system. In Basal Ganglia and Movement disorders. Bignami. A. (ed).NINS Vol. III. Thieme. Stuttgart pp. 211–234
- Percheron, G. (2003) Thalamus. In The human nervous system. Paxinos, G. and Mai, J. eds) Elsevier, Amsterdam
- Percheron, G., Fénelon, G., Leroux-Hugon, V. and Fève, A. (1994) Histoire du système des ganglions de la base. Rev. Neurol. 150:543-554
- Percheron, G. and Filion, M. (1991) Parallel processing in the basal ganglia : up to a point. Trends Neurosci. 14: 55-59
- Percheron, G.,François, C, Parent, A.Sadikot, A.F., Fenelon, G. and Yelnik, J. (1991) The primate central complex as one of the basal ganglia. In The Basal Ganglia III Bernardi, G. et al. (eds) pp. 177–186. Plenum . New York
- Percheron, G., François, C., Talbi, B., Meder, J_F, Yelnik, J., Fenelon, G. (1996) The primate motor thalamus. Brain Res. Rev. 22: 93-181
- Percheron, G., François, C. and Yelnik, J.(1987) Spatial organization and information processing in the core of the basal ganglia. in Carprenter, M.B., Jayaraman, A.(eds) The basal Ganglia II.Plenum, Adv. Behav. Biol. 32 pp. 205–226.
- Percheron, G., François, C.,Yelnik, J., Fenelon, G. (1989) The primate nigro-striato-pallido-nigral system . Not a mere loop. In Crossman, A.R and Sambrook, M.A (eds)Neural mechanisms in disorders of movements. Libey, London
- Percheron, G., François, C. and Yelnik, J. and Fenelon, G.(1994) The basal ganglia related system of primates: definition, description and informational analysis. In Percheron, G., McKenzie, J.S., Feger, J. (eds) The basal ganglia IV. Plenum Press New York pp. 3–20
- Percheron, G., Yelnik, J., François, C. (1984) A Golgi analysis of the primate ganglia III. Spatial organization of the striatopallidal complex. J. Comp. Neurol. 227: 214-227
- Plenz, D., Kitai, S.T. (1999) A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus. Nature 400: 677-682
- Prensa, L., Cosette, M., Parent, A. (2000) Dopaminergic innervation of human basal ganglia. J. Chem. Anat. 20: 207-213
- Sato, F., Lavallée, P., Levesque, M. and Parent, A. (2000) Single-axon tracing study of neurons of the external segment of the globus pallidus in primate. J. Comp. Neurol. 417: 17-31
- Sato, F., Parent, M., Levesque, M., Parent, A.(2000) Axonal branching patterns of neurons of subthalamic neurons in primates. J. Comp. Neurol. 14: 142-152
- Selemon, L.D. and Goldman Rakic, P.S. (1985) Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J. Neurosci. 5: 776-794
- Surmeier, D.J., Mercer, J.N. and Savio Chan, C. (2005) Autonomous pacemakers in the basal ganglia: who needs excitatory synapses anyway? Cur. Opin. Neurobiol. 15:312-318.
- Terminologia anatomica (1998) Thieme, Stuttgart
- Tremblay, L. and Filion, M. (1989) Responses of pallidal neurons to striatal stimulation in intact waking monkeys. Brain Res. 498: 1-16
- Tremblay, L., Filion, M. and Bédard, P.J. (1988) Responses of pallidal neurons to striatal stimulation in monkeys with MPTP-induced parkinsonism. Brain Res. 498: 17-33
- Vicq d'Azyr , (1786)
- Vogt, C. and O. (1941)
- Wichmann, T. and Kliem, M.A. (2002) Neuronal activity in the primate substantia nigra pars reticulata during the performance of simple and memory-guided elbow movements. J. Neurophysiol. 91: 815-827 PMID
- Yelnik, J., François, C., Percheron, G., Heyner, S. (1987) Golgi study of the primate substantia nigra. I. Quanttitative morphology and typology of nigral neurons. J. Comp. Neurol. 265: 455-472
- Yelnik, J., François, Percheron, G., Tandé, D. (1991) Morphological taxonomy of the neurons of the primate striatum. J. Comp. Neurol. 313:273 .
- Yelnik, J. and Percheron, G. (1979) Subthalamic neurons in primates: a quantitative and comparative analysis. Neuroscience 4:1717-1743