Zona incerta
Encyclopedia
The zona incerta is a horizontally elongated region of gray matter
cells in the subthalamus
below the thalamus
. Its connections project extensively over the brain
from the cerebral cortex
down into the spinal cord
.
Its function is unknown though several have been proposed related to “limbic–motor integration” such as controlling visceral activity and pain; gating sensory input and synchronizing cortical and subcortical brain rhythms. Its dysfunction may play a role in central pain syndrome
. It is also been identified as a promising deep brain stimulation
therapy target for treating Parkinsons Disease.
Its existence was first described by Auguste Forel in 1877 as a “region of which nothing certain can be said”. A hundred and thirty years later in 2007, Nadia Urbain and Martin Deschênes of Université Laval
noted that the “zona incerta is among the least studied regions of the brain; its name does not even appear in the index of many textbooks.”
is located medially
to the internal capsule
, ventral to the thalamus
, and is contiguous with the thalamic reticular nucleus. The nucleus separates the lenticular fasciculus
from the thalamic fasciculus
(also known as the “field H1 of Forel”) .
Its cells are very heterogeneous differing widely in their shape and size. Its chemoarchitecture is also diverse containing up to 20 different types of neurochemically defined cells. It has been noted that "There are few diencephalic regions that have as much cellular and neurochemical diversity".
In rats four areas are usually identified.
These areas lack clear cell-free borders and merge into each other.
Zona incerta neurons have dendrites with a wide span 0.8 mm and their axons give off collaterals that arborized locally within the zona incerta providing a means for lateral inhibition
. The ventral area of the zona incerta has been described as having “a network of GABAergic
cells with widespread interconnections, so that cells in one subsector may influence the activity of cells in a different subsector”.
The zona incerta together with the hypothalamus is one of the two areas of the brain that produces the neuropeptide melanin concentrating hormone
. Dopaminergic
ones are also more prevalent. There are in addition populations of cells producing somatostatin
, angiotensin II and melanocyte stimulating hormone.
, diencephalon
, basal ganglia
, brainstem and spinal cord
.
Cerebral cortex
Projections to the zona incerta arise across the cortical mantel from the frontal
to the occipital lobe
s. The heaviest projections are from cingulate cortex
, frontal and parietal
areas. The head area of the body seems from these areas to have the largest representation in the zona incerta. These projections preferentially go to cortical layer I neurons. There are projections from the zona incerta back to the cerebral cortex.
Diencephalon
Projections with the diencephalon are reciprocal and mainly to the thalamus
such as the intralaminar nucleus
(parafascicular nucleus and central lateral nucleus) and higher-order nuclei such as the lateral posterior nucleus. The zona incerta avoids the thalamus nuclei of the primary sensory areas such as the ventral posterior nucleus
of the somatosensory system and the lateral geniculate of the visual system.
Hypothalamus
Projections to the hypothalamus go mainly to the paraventricular nucleus areas in the anterior hypothalamus
, lateral hypothalamus
, lateral preoptic area
, horizontal diagonal band of Broca
, and the parvocellular region of the paraventricular nucleus.
Basal ganglia
Zona incerta is connected in the basal ganglia to the substantia nigra
(both pars compacta
and pars reticulata
) and pedunculopontine tegmental nucleus (but only its pars dissipata area). It also has less important connections to the entopeduncular nucleus and globus pallidus
. These projections are glutamatergic and excitatory rather than GABAergic and inhibitory. The zona incerta also receives input from these areas.
Brainstem
Zona incerta receives input from many parts of the brainstem nuclei including the periaqueductal gray
, raphe nuclei
, thalamic reticular nucleus, and the deep layers of the superior colliculus
. It is regulated by inputs from brainstem cholinergic
nuclei such as the Laterodorsal tegmental nucleus
and pedunculopontine nucleus
upon its neuron’s muscarinic receptors.
Spinal cord
Zona incerta afferents terminate within the spinal cord
gray matter, particularly the anterior horn
, while spinal projections back to the zona incerta arise from cells located across the posterior horn and intermediate gray
.
Other
Zona incerta also has connections to the amygdala
, basal forebrain
, the osmoreceptor
s in the subfornical organ
, olfactory bulb
, posterior pituitary
and habenula
.
Some of these projections appear in register; the representation of the same body part in cortex and spinal cord connect to the same areas in the zona incerta. This is possibly so with the superior colliculus.
Visceral survival activities.
Zona incerta controls such activities as water and food intake, sexuality and cardiovascular activity. This control is related to its effects upon the nearby posterior hypothalamus
with which it shares similar connections and neurochemically defined cell types.
The zona incerta receives pain input through the spinothalamic tract
and this has been shown to control the activity of the pain transmission pathway in the posterior thalamus.
Electrical or chemical stimulation of the zona incerta creates limbic-related movements, such as those associated with defense orientation and copulation.
Sensory-motor activities.
At rest sensory input to the higher sensory areas of the cerebral cortex is gated through the thalamus. It has moreover been proposed that the zona incerta provides a top-down disinhibitory mechanism of this gating when there is sensory-motor activity such as the tactile use of whisker
s.
This has also been linked to sensory gating changes between sleep and waking. In this occurs a zona incerta mediated inhibition of thalamic nuclei such the somatosensory posterior medial thalamus. This is most strong when cholinergic
input to the zona incerta is reduced as during slow-wave sleep
and during anesthesia
. The consequence of this has been explained upon information processing:
The zona incerta projects to the superior colliculus
and these link to the initiation of orientating eye and head movements. In monkeys for example neuronal activity in the zona incerta “pauses” before the start of a saccade and resumes at the end of a saccade.
Synchronizing cortical and subcortical brain rhythms and integration.
The GABAergic input received from the cerebral cortex has been suggested to synchronize thalamocortical and brainstem rhythms by providing a link between basal ganglia output and the cerebello-thalamo cortical loop. This allows it to synchronize oscillations generate by the basal ganglia during the preparation and execution of intended movements. One function of the loop is to carry movement instructions to the motor cortex through zona incerta output to the ventral lateral nucleus
neurons in the cerebello-thalamocortical loop and to brainstem motor neurons in the medial reticular formation and midbrain extrapyramidal
area. This acts to synchronize the basal ganglia areas involved in planning and execution of the movement with those in the brainstem controlling axial and proximal limb
muscles with those areas in the motor cortex that control distal limb movements.
Synthesis
John Mitrofanis at the University of Sydney
has proposed a general theory that might underlie some of the above.
Deep brain stimulation
of the subthalamic nucleus in those with Parkinson Disease has identified the zona incerta as a promising target area for effective therapy. Unlike deep bilateral stimulation of the ventral lateral nucleus
such stimulation of the zona incerta improves all aspects of tremor
including both the distal and proximal parts of limbs and the body more generally. This also occurs without dysarthria
and disequilibrium
as this stimulation does not interrupt proprioceptive sensation and the processing of the fine motor skill
movements of vocal cords.
Researchers observed that “The ventral lateral nucleus has long been established as an effective surgical target for controlling distal limb tremor, including Parkinson Disease tremor. However, because it receives predominantly cerebellar afferents and no direct basal ganglia afferents, the reason why it is effective in controlling Parkinson Disease tremor has remained a paradox. The conduction of abnormal oscillations generated in the basal ganglia in Parkinson Disease to the ventral lateral nucleus via zona incerta would therefore explain this paradox and also explain why we observed such a potent anti-tremor effect from stimulating zona incerta in our patients with Parkinson Disease”
The study further noted that deep brain stimulation upon the zona incerta “is effective in suppressing all components of tremor affecting both the distal and proximal part of the body. These results, if replicated in larger randomised controlled studies, have important implications for our current surgical management of patients with tremor and point to a more promising target area than the ventral lateral nucleus of the thalamus.”
is pain
initiated or caused by injury or dysfunction in the central nervous system
. Recent research suggests that the development and maintenance of such pain could link to abnormal inhibitory regulation by the zona incerta of the posterior thalamus. It has been suggested that there exists
Gray Matter
"Gray Matter" is a short story by Stephen King, first published in the October 1973 issue of Cavalier magazine, and later collected in King's 1978 collection Night Shift. It is set in the same area as King's novel Dreamcatcher.-Setting:...
cells in the subthalamus
Subthalamus
The subthalamus is a part of the diencephalon. Its major part is the subthalamic nucleus. Functionally, it also encompasses the globus pallidus, which is topographically part of the telencephalon.-Anatomy:...
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...
. Its connections project extensively over the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
from the cerebral cortex
Cerebral 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...
down into the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
.
Its function is unknown though several have been proposed related to “limbic–motor integration” such as controlling visceral activity and pain; gating sensory input and synchronizing cortical and subcortical brain rhythms. Its dysfunction may play a role in central pain syndrome
Central pain syndrome
Central pain syndrome is a neurological condition caused by damage or malfunction in the Central Nervous System which causes a sensitization of the pain system. The extent of pain and the areas affected are related to the cause of the injury, which can include trauma, tumors, stroke, Multiple...
. It is also been identified as a promising deep brain stimulation
Deep brain stimulation
Deep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
therapy target for treating Parkinsons Disease.
Its existence was first described by Auguste Forel in 1877 as a “region of which nothing certain can be said”. A hundred and thirty years later in 2007, Nadia Urbain and Martin Deschênes of Université Laval
Université Laval
Laval University is the oldest centre of education in Canada and was the first institution in North America to offer higher education in French...
noted that the “zona incerta is among the least studied regions of the brain; its name does not even appear in the index of many textbooks.”
Anatomy
This nucleusNucleus (neuroanatomy)
In neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
is located medially
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
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....
, ventral to 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...
, and is contiguous with the thalamic reticular nucleus. The nucleus separates the lenticular fasciculus
Lenticular fasciculus
The lenticular fasciculus is a tract connecting the globus pallidus to the Thalamic fasciculus. The thalamic fasciculus runs into the Thalamus...
from the thalamic fasciculus
Thalamic fasciculus
The thalamic fasciculus is a component of the subthalamus. It is sometimes considered synonymous with "field H1 of Forel". Nerve fibres forming a composite bundle containing cerebellothalamic and pallidothalamic fibres that is insinuated between the thalamus and zona incerta.The thalamic...
(also known as the “field H1 of Forel”) .
Its cells are very heterogeneous differing widely in their shape and size. Its chemoarchitecture is also diverse containing up to 20 different types of neurochemically defined cells. It has been noted that "There are few diencephalic regions that have as much cellular and neurochemical diversity".
In rats four areas are usually identified.
- a rostral sector that has densely packed spindle-shaped cells and scattered larger oval shaped cells.
- a dorsal sector that has medium-sized oval-shaped cells.
- a ventral sector made up of medium-sized multipolar or fusiform shaped cells that are more densely packed than the cells in the dorsal sector
- a caudal sector made up of small and medium-sized somata that are either multipolar, fusiform or rounded in shape, together with a group of very large multipolar-shaped cells located medially. This is sometimes called the motor part of the zona incerta nucleus. This is the area targeted by deep brain stimulation area when the zona incerta is targeted in the treatment of Parkinson Disease.
These areas lack clear cell-free borders and merge into each other.
Zona incerta neurons have dendrites with a wide span 0.8 mm and their axons give off collaterals that arborized locally within the zona incerta providing a means for lateral inhibition
Lateral inhibition
In neurobiology, lateral inhibition is the capacity of an excited neuron to reduce the activity of its neighbors. Lateral inhibition sharpens the spatial profile of excitation in response to a localized stimulus.-Sensory inhibition:...
. The ventral area of the zona incerta has been described as having “a network of GABAergic
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
cells with widespread interconnections, so that cells in one subsector may influence the activity of cells in a different subsector”.
The zona incerta together with the hypothalamus is one of the two areas of the brain that produces the neuropeptide melanin concentrating hormone
Melanin concentrating hormone
Melanin-concentrating hormone is a cyclic 19-amino acid orexinogenic hypothalamic peptide originally isolated from the pituitary gland of teleost fish where it controls skin pigmentation....
. 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...
ones are also more prevalent. There are in addition populations of cells producing somatostatin
Somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
, angiotensin II and melanocyte stimulating hormone.
Connections
The zona incerta has connections to 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...
, diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and 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...
, brainstem and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
.
Cerebral cortex
Projections to the zona incerta arise across the cortical mantel from the frontal
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...
to the occipital lobe
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...
s. The heaviest projections are from cingulate cortex
Cingulate cortex
The cingulate cortex is a part of the brain situated in the medial aspect of the cortex. It includes the cortex of the cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cingulate sulcus...
, frontal and parietal
Parietal lobe
The parietal lobe is a part of the Brain positioned above the occipital lobe and behind the frontal lobe.The parietal lobe integrates sensory information from different modalities, particularly determining spatial sense and navigation. For example, it comprises somatosensory cortex and the...
areas. The head area of the body seems from these areas to have the largest representation in the zona incerta. These projections preferentially go to cortical layer I neurons. There are projections from the zona incerta back to the cerebral cortex.
Diencephalon
Projections with the diencephalon are reciprocal and mainly to 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...
such as the intralaminar nucleus
Intralaminar nucleus
The intralaminar nucleus is a nucleus of the thalamus that contains the following nuclei:* central lateral* centromedian * paracentral* parafascicular.Some sources also include a "central dorsal" nucleus....
(parafascicular nucleus and central lateral nucleus) and higher-order nuclei such as the lateral posterior nucleus. The zona incerta avoids the thalamus nuclei of the primary sensory areas such as the ventral posterior nucleus
Ventral posterior nucleus
The ventral posterior nucleus is the somato-sensory relay nucleus in thalamus of the brain.-Input and output:The ventral posterior nucleus receives neuronal input from the medial lemniscus, spinal lemniscus, spinothalamic tracts, and trigeminothalamic tract...
of the somatosensory system and the lateral geniculate of the visual system.
Hypothalamus
Projections to the hypothalamus go mainly to the paraventricular nucleus areas in the anterior hypothalamus
Anterior hypothalamic nucleus
The anterior hypothalamic nucleus is a nucleus of the hypothalamus.Its function is thermoregulation of the body.The anterior hypothalamus plays a role in regulating sleep....
, lateral hypothalamus
Lateral hypothalamus
The lateral hypothalamus or lateral hypothalamic area is a part of the hypothalamus.It is concerned with hunger. Damage to this area can cause reduced food intake...
, lateral preoptic area
Preoptic area
The preoptic area is a region of the hypothalamus. According to the MeSH classification, it is considered part of the anterior hypothalamus. There are four nuclei in this region, according to Terminologia Anatomica .-Functions:The preoptic area is responsible for thermoregulation and receives...
, horizontal diagonal band of Broca
Diagonal band of Broca
The diagonal band of Broca forms the medial margin of the anterior perforated substance.-Contents:It consists of fibers that are said to arise in the parolfactory area, the gyrus subcallosus and the anterior perforated substance, and course backward in the longitudinal striae to the dentate gyrus...
, and the parvocellular region of the paraventricular nucleus.
Basal ganglia
Zona incerta is connected in the basal ganglia 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...
(both pars compacta
Pars 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...
and 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 pedunculopontine tegmental nucleus (but only its pars dissipata area). It also has less important connections to the entopeduncular nucleus and 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...
. These projections are glutamatergic and excitatory rather than GABAergic and inhibitory. The zona incerta also receives input from these areas.
Brainstem
Zona incerta receives input from many parts of the brainstem nuclei including the periaqueductal gray
Periaqueductal gray
Periaqueductal gray is the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain. It plays a role in the descending modulation of pain and in defensive behaviour...
, raphe nuclei
Raphe nuclei
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...
, thalamic reticular nucleus, and the deep layers of the superior colliculus
Superior 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...
. It is regulated by inputs from brainstem 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...
nuclei such as the Laterodorsal tegmental nucleus
Laterodorsal tegmental nucleus
The laterodorsal tegmental nucleus is a nucleus situated in the brainstem, spanning the midbrain tegmentum and the pontine tegmentum...
and pedunculopontine nucleus
Pedunculopontine nucleus
The pedunculopontine nucleus is located in the brainstem, caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. It has two divisions, one containing cholinergic neurons, the pars compacta, and one containing mostly glutamatergic neurons, the pars dissipata...
upon its neuron’s muscarinic receptors.
Spinal cord
Zona incerta afferents terminate within the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
gray matter, particularly the anterior horn
Anterior horn (spinal cord)
The anterior horn of the spinal cord is the ventral grey matter section of the spinal cord. The anterior horn contains motor neurons that affect the axial muscles while the posterior horn receives information regarding touch and sensation...
, while spinal projections back to the zona incerta arise from cells located across the posterior horn and intermediate gray
Anterior spinothalamic tract
The ventral spinothalamic fasciculus situated in the marginal part of the anterior funiculus and intermingled more or less with the vestibulo-spinal fasciculus, is derived from cells in the posterior column or intermediate gray matter of the opposite side...
.
Other
Zona incerta also has connections to 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.-...
, basal forebrain
Basal forebrain
The basal forebrain is a collection of structures located ventrally to the striatum. It is considered to be the major cholinergic output of the central nervous system . It includes a group of structures that lie near the bottom of the front of the brain, including the nucleus basalis, diagonal band...
, the osmoreceptor
Osmoreceptor
An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including the organum vasculosum of the lamina terminalis and the subfornical organ...
s in the subfornical organ
Subfornical organ
The subfornical organ, situated on the ventral surface of the fornix, at the interventricular foramina , is one of the circumventricular organs of the brain.-Relations with other circumventricular organs:...
, olfactory bulb
Olfactory bulb
The olfactory bulb is a structure of the vertebrate forebrain involved in olfaction, the perception of odors.-Anatomy:In most vertebrates, the olfactory bulb is the most rostral part of the brain. In humans, however, the olfactory bulb is on the inferior side of the brain...
, posterior pituitary
Posterior pituitary
The posterior pituitary comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland, per se; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior...
and habenula
Habenula
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...
.
Some of these projections appear in register; the representation of the same body part in cortex and spinal cord connect to the same areas in the zona incerta. This is possibly so with the superior colliculus.
Functions
The function of the Zona incerta is unknown, “To this day, we are still not certain of the precise function of this 'zone of uncertainty'” However it is suggested to have possible roles in “limbic–motor integration”.Visceral survival activities.
Zona incerta controls such activities as water and food intake, sexuality and cardiovascular activity. This control is related to its effects upon the nearby posterior hypothalamus
Posterior nucleus (hypothalamus)
The posterior nucleus of the hypothalamus is one of the many nuclei that make up the hypothalamic region of the brain.Its function is thermoregulation of the body.Damage or destruction of this nucleus causes hypothermia...
with which it shares similar connections and neurochemically defined cell types.
The zona incerta receives pain input through the spinothalamic tract
Spinothalamic tract
The spinothalamic tract is a sensory pathway originating in the spinal cord. It transmits information to the thalamus about pain, temperature, itch and crude touch...
and this has been shown to control the activity of the pain transmission pathway in the posterior thalamus.
Electrical or chemical stimulation of the zona incerta creates limbic-related movements, such as those associated with defense orientation and copulation.
Sensory-motor activities.
At rest sensory input to the higher sensory areas of the cerebral cortex is gated through the thalamus. It has moreover been proposed that the zona incerta provides a top-down disinhibitory mechanism of this gating when there is sensory-motor activity such as the tactile use of whisker
Whisker
Whisker may refer to:* an element of box plots* cat's whisker diode, a thin wire used as a contact on a crystal radio receiver* facial hair, hair on the face of a human* vibrissa, a hair on the face of a mammal, used for sensing the surroundings...
s.
This has also been linked to sensory gating changes between sleep and waking. In this occurs a zona incerta mediated inhibition of thalamic nuclei such the somatosensory posterior medial thalamus. This is most strong when 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...
input to the zona incerta is reduced as during slow-wave sleep
Slow-wave sleep
Slow-wave sleep , often referred to as deep sleep, consists of stages 3 and 4 of non-rapid eye movement sleep, according to the Rechtschaffen & Kales standard of 1968. As of 2008, the American Academy of Sleep Medicine has discontinued the use of stage 4, such that the previous stages 3 and 4 now...
and during anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
. The consequence of this has been explained upon information processing:
As a result, posterior medial thalamus neurons fail to respond to ascending sensory inputs, and function primarily in “higher-order” mode, concerned with relaying trans-cortical information. By contrast, increased cholinergic activity during wakefulness and enhanced vigilance suppresses zona incerta -mediated inhibition, thereby ungating posterior thalamus responses to ascending inputs.
The zona incerta projects to the superior colliculus
Superior 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...
and these link to the initiation of orientating eye and head movements. In monkeys for example neuronal activity in the zona incerta “pauses” before the start of a saccade and resumes at the end of a saccade.
Synchronizing cortical and subcortical brain rhythms and integration.
The GABAergic input received from the cerebral cortex has been suggested to synchronize thalamocortical and brainstem rhythms by providing a link between basal ganglia output and the cerebello-thalamo cortical loop. This allows it to synchronize oscillations generate by the basal ganglia during the preparation and execution of intended movements. One function of the loop is to carry movement instructions to the motor cortex through zona incerta output to the ventral lateral nucleus
Ventral lateral nucleus
-Inputs and outputs:It receives neuronal inputs from the basal ganglia which includes the substantia nigra and the globus pallidus . It also has inputs from the cerebellum ....
neurons in the cerebello-thalamocortical loop and to brainstem motor neurons in the medial reticular formation and midbrain extrapyramidal
Extrapyramidal system
In human anatomy, the extrapyramidal system is a neural network located in the brain that is part of the motor system involved in the coordination of movement. The system is called "extrapyramidal" to distinguish it from the tracts of the motor cortex that reach their targets by traveling through...
area. This acts to synchronize the basal ganglia areas involved in planning and execution of the movement with those in the brainstem controlling axial and proximal limb
muscles with those areas in the motor cortex that control distal limb movements.
Synthesis
John Mitrofanis at the University of Sydney
University of Sydney
The University of Sydney is a public university located in Sydney, New South Wales. The main campus spreads across the suburbs of Camperdown and Darlington on the southwestern outskirts of the Sydney CBD. Founded in 1850, it is the oldest university in Australia and Oceania...
has proposed a general theory that might underlie some of the above.
The zona incerta is in a position to form a primal synaptic interface of the diencephalon, linking diverse sensory channels to appropriate visceral, arousal, attention and posture-locomotion responses. The different sensory inputs, whether exteroreceptive (somatic) or interoreceptive (visceral), influence these activities by driving zona incerta cells with different projection patterns and functions; each of these cells may be located in different sectors of the zone… In essence, it is suggested that the zona incerta has the pathways to integrate both exteroreceptive (e.g. somatosensory) and interoreceptive (e.g. thirst) sensory challenges, so that visceral activity, arousal, attention and/or posture locomotion are altered and/or generated. The zona incerta could form a neural niche in the thalamus from where these responses are “recruited” immediately, as to give an instant response.
Parkinsons Disease
Parkinsons Disease might disrupt the zona incerta as it is hyperactive in parkinsonian experimental animals. In humans with Parkinsons Disease, surgical lesion of the zona incerta alleviates their parkinsonian motor symptoms.Deep brain stimulation
Deep brain stimulation
Deep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
of the subthalamic nucleus in those with Parkinson Disease has identified the zona incerta as a promising target area for effective therapy. Unlike deep bilateral stimulation of the ventral lateral nucleus
Ventral lateral nucleus
-Inputs and outputs:It receives neuronal inputs from the basal ganglia which includes the substantia nigra and the globus pallidus . It also has inputs from the cerebellum ....
such stimulation of the zona incerta improves all aspects of tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
including both the distal and proximal parts of limbs and the body more generally. This also occurs without dysarthria
Dysarthria
Dysarthria is a motor speech disorder resulting from neurological injury of the motor component of the motor-speech system and is characterized by poor articulation of phonemes...
and disequilibrium
Disequilibrium (medicine)
In medicine, disequilibrium refers to an impaired sense of equilibrioception.It is one of the causes of dizziness.It is caused by the lesioof the vestibulocerebellar tract.-References:Otology...
as this stimulation does not interrupt proprioceptive sensation and the processing of the fine motor skill
Fine motor skill
Fine motor skills are the coordination of small muscle movements which occur e.g., in the fingers, usually in coordination with the eyes. In application to motor skills of hands the term dexterity is commonly used....
movements of vocal cords.
Researchers observed that “The ventral lateral nucleus has long been established as an effective surgical target for controlling distal limb tremor, including Parkinson Disease tremor. However, because it receives predominantly cerebellar afferents and no direct basal ganglia afferents, the reason why it is effective in controlling Parkinson Disease tremor has remained a paradox. The conduction of abnormal oscillations generated in the basal ganglia in Parkinson Disease to the ventral lateral nucleus via zona incerta would therefore explain this paradox and also explain why we observed such a potent anti-tremor effect from stimulating zona incerta in our patients with Parkinson Disease”
The study further noted that deep brain stimulation upon the zona incerta “is effective in suppressing all components of tremor affecting both the distal and proximal part of the body. These results, if replicated in larger randomised controlled studies, have important implications for our current surgical management of patients with tremor and point to a more promising target area than the ventral lateral nucleus of the thalamus.”
Central pain syndrome
Central pain syndromeCentral pain syndrome
Central pain syndrome is a neurological condition caused by damage or malfunction in the Central Nervous System which causes a sensitization of the pain system. The extent of pain and the areas affected are related to the cause of the injury, which can include trauma, tumors, stroke, Multiple...
is pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
initiated or caused by injury or dysfunction in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. Recent research suggests that the development and maintenance of such pain could link to abnormal inhibitory regulation by the zona incerta of the posterior thalamus. It has been suggested that there exists
a significant suppression of both spontaneous and evoked activity in inhibitory neurons in zona incerta and abnormally high spontaneous and evoked activity of neurons in posterior thalamus in animals with central pain syndrome. The positive association between behavioral and neurophysiological thresholds in rats with central pain syndrome is consistent with a causal role for suppressed incerto-thalamic inputs in central pain syndrome.
External links
- http://isc.temple.edu/neuroanatomy/lab/atlas/pdhn/