Mesolimbic pathway
Encyclopedia
Dopaminergic pathways
Dopaminergic pathways are neural pathways in the brain which transmit the neurotransmitter dopamine from one region of the brain to another.The neurons of the dopaminergic pathways have axons which run the entire length of the pathway...
in 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,...
. The pathway begins in the ventral tegmental area
Ventral tegmentum
The ventral tegmentum , better known as the ventral tegmental area , is a group of neurons located close to the midline on the floor of the midbrain...
of the midbrain
Mesencephalon
The midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....
and connects to the limbic system
Limbic system
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...
via the nucleus accumbens
Nucleus accumbens
The 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...
, 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.-...
, and the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
as well as to the medial prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
. The mesolimbic dopamine system is widely believed to be a "reward" pathway, but that theory is not universally accepted.
Anatomy
The following structures are considered to be a part of the mesolimbic pathway:Ventral Tegmental Area
- The ventral tegmental area (VTA) is a part of the midbrain. It consists of dopaminergic, GABAergicGABA receptorThe GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
, and glutamatergicGlutamic acidGlutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
neuronNeuronA neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s. The VTA communicates with the nucleus accumbens via the unmyelinated medial forebrain bundleMedial forebrain bundleThe Medial forebrain bundle , is a complex bundle of axons coming from the basal olfactory regions, the periamygdaloid region, and the septal nuclei.-Anatomy:...
.
Nucleus Accumbens
- The nucleus accumbens is found in the ventral 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...
and is composed of medium spiny neuronMedium spiny neuronThe medium spiny neurons are a special type of inhibitory cells representing approximately 90% of the neurons within the corpus striatum of the basal ganglia. They play a key role in initiating and controlling movements of the body, limbs, and eyes....
s. It is subdivided into limbic and motor subregions known as the shell and core. The medium spiny neurons receive input from both the dopaminergic neurons of the VTA and the glutamatergic neurons of the hippocampus, amygdala, and medial prefrontal cortex. When they are activated by these inputs, the medium spiny neurons' projections release GABA onto the ventral pallidumGlobus pallidusThe 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...
. The release of dopamine in this structure drives the mesolimbic system.
Amygdala
- The amygdala is a large nuclear mass in the temporal lobeTemporal lobeThe temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
anterior to the hippocampus. It has been associated with the assignment of emotions, especially fear and anxiety. There are two, one in each temporal lobe, and their functions may be lateralizedLateralization of brain functionA longitudinal fissure separates the human brain into two distinct cerebral hemispheres, connected by the corpus callosum. The sides resemble each other and each hemisphere's structure is generally mirrored by the other side. Yet despite the strong anatomical similarities, the functions of each...
.
Hippocampus
- The hippocampus is located in the medial portion of the temporal lobe. It is known for its association with double memory .
Bed Nucleus of the Stria Terminalis
Controversy over mesolimbic dopamine function
There is some controversy regarding dopamineDopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
’s role in the reward system
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
. Three hypotheses — hedonia, learning, and incentive salience — have been proposed as explanations for dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
’s function in the reward system
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
. The hedonia hypothesis suggests that dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
in the nucleus accumbens
Nucleus accumbens
The 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...
acts as a 'pleasure
Pleasure
Pleasure describes the broad class of mental states that humans and other animals experience as positive, enjoyable, or worth seeking. It includes more specific mental states such as happiness, entertainment, enjoyment, ecstasy, and euphoria...
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...
'. Historically, in the late 1970s, it was found that some drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s of abuse involved dopamine activity, particularly in the nucleus accumbens
Nucleus accumbens
The 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...
, to cause the "high" or euphoric
Euphoria (emotion)
Euphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of well-being, elation, happiness, ecstasy, excitement and joy...
state. However, not all rewards or pleasurable things involve activation of the reward system, which may suggest that the mesolimbic pathway may not be just a system that works merely off enjoyable things (hedonia). Learning, on the other hand, deals with predictions of future rewards and association formation. Studies have shown that rats that had their ventral tegmental area and nucleus accumbens
Nucleus accumbens
The 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...
destroyed do not lose their learning capabilities, but rather lack the motivation
Motivation
Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...
to work for a reward. Incentive salience
Incentive salience
Incentive salience is a motivational "wanting" attribute given by the brain to reward-predicting stimuli. This "wanting" is unlike "liking" in that liking is a pleasure immediately gained from consumption or other contact with stimuli, while the "wanting" of incentive salience is a motivational...
(wanting) stands out as a possible role for dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
as it regards this molecule as being released when there is a stimulus worth working hard for, thus making an individual work to get it. This is one of the reasons why dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
transport has been extensively studied in the case of ADD
ADD
* A.D.D. , a song on System of a Down's album Steal This Album!* A.D.D. , the first studio album by Blake Lewis, the runner-up on the sixth season of American Idol...
and ADHD. It is now widely understood that most people suffering from some form of attention deficit disorder most likely lack dopamine stimulation. This also explains why dopamine reuptake inhibitors and stimulants often dramatically improve symptoms of attention disorders. In self-administration studies, animals have been trained to give an operant response
Operant conditioning
Operant conditioning is a form of psychological learning during which an individual modifies the occurrence and form of its own behavior due to the association of the behavior with a stimulus...
(lever press, nose poke, wheel turn, etc.) in order to obtain either a drug or mate. It has been shown that the animals will continue to perform the required task until the reward is received, or fatigue sets in.
Clinical significance
Since the mesolimbic pathway is shown to be associated with feelings of reward and desire, this pathway is heavily implicated in neurobiological theories of addictionSubstance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
, schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, and depression.
Drug addiction, the loss of control over drug use or the compulsive seeking and taking of drugs despite adverse consequences, with the four major classes of abused drugs (psychostimulants, opiates, ethanol, and nicotine) are due to increased dopamine transmission in the limbic system-each by different mechanisms. Like drug addiction, schizophrenia and depression have similar structural changes with dopamine transmission.
Other dopamine pathways
The other dopamine pathways are:- mesocortical pathwayMesocortical pathwayThe mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...
- nigrostriatal pathwayNigrostriatal pathwayThe nigrostriatal pathway is a neural pathway that connects the substantia nigra with the striatum. It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop.Loss of dopamine...
- tuberoinfundibular pathwayTuberoinfundibular pathwayThe tuberoinfundibular pathway refers to a population of dopamine neurons in the arcuate nucleus of the mediobasal hypothalamus that project to the median eminence . It is one of the four major dopamine pathways in the brain...
External links
- Diagram at Utah.edu