Anatomy

In humans, the nerve cell bodies of the pars compacta are coloured black by the pigment

Pigment

A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...

 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 particularly long and thick dendrites (François et al.). The ventral dendrites, particularly, go down deeply in 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...

. Other similar neurons are more sparsely distributed in the mesencephalon and constitute "groups" with no clear borders, although continuous to the pars compacta, in a prerubral position. These have been given, in early works in rats (with not much respect for the anatomical subdivisions), the name of "area A8" and "A10". The pars compacta itself ("A9") is usually subdivided into a ventral and a dorsal tier, the last being 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...

 positive. The ventral tier is considered as A9v. The dorsal tier A9d is linked to an ensemble comprising also A8 and A10, A8, A9d and A10 representing 28% of dopaminergic neurons. The long dendrites of compacta neurons receive striatal information. This cannot be the case for the more posterior groups that are located outside the striato-pallidonigral bundle territory. Neurons of the pars compacta receive inhibiting signals from the collateral axons from the neurons of the pars reticulata. All these neurons send their 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 along the nigrostriatal pathway

Nigrostriatal pathway

The 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...

 to 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...

 where they release the 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...

 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...

. There is an organization in which dopaminergic neurons of the fringes (the lowest) go to the sensorimotor striatum and the highest to the associative striatum. Dopaminergic axons also innervate other elements of the basal ganglia system including the lateral and medial pallidum, substantia nigra pars reticulata, and the 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...

.

Function

The function of the dopamine neurons in the substantia nigra pars compacta is complex. Contrary to what was thought initially it is not directly linked to movements. "Dopamine neurons are activated by novel, unexpected stimuli, by primary rewards in the absence of predictive stimuli and during learning". Dopamine neurons are thought to be involved in learning to predict which behaviours will lead to a reward (for example food

Food

Food is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals...

 or sex

Sex

In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...

). In particular, it is suggested that dopamine neurons fire when a reward is greater than that previously expected; a key component of many reinforcement learning models. This signal can then be used to update the expected value of that action. Many drugs of abuse, such as cocaine

Cocaine

Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, mimic this reward response—providing an explanation for their addictive

Substance 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:...

 nature.

Pathology

Degeneration of pigmented neurons in this region is the principal pathology

Pathology

Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....

 that underlies Parkinson's disease

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system...

. In a few people, the cause of Parkinson's disease is genetic

Genetics

Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

, but in most cases, the reason for the death of these dopamine neurons is unknown. Parkinsonism

Parkinsonism

Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...

 can also be produced by viral infections such as encephalitis

Encephalitis

Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

 or a number of toxins, such as MPTP

MPTP

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...

, an industrial toxin which can be mistakenly produced during synthesis of the meperidine analog MPPP

MPPP

1-Methyl-4-phenyl-4-propionoxypiperidine or Desmethylprodine is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche. It is not used in clinical practice, but has been illegally manufactured for recreational drug use...

. Many such toxins appear to work by producing reactive oxygen species

Reactive oxygen species

Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

. Binding to neuromelanin by means of charge transfer complex

Charge transfer complex

A charge-transfer complex or electron-donor-acceptor complex is an association of two or more molecules, or of different parts of one very large molecule, in which a fraction of electronic charge is transferred between the molecular entities. The resulting electrostatic attraction provides a...

es may concentrate radical-generating toxins in the substantia nigra.

Pathological changes to the dopaminergic neurons of the pars compacta are also thought to be involved in 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...

 (see the dopamine hypothesis of schizophrenia

Dopamine hypothesis of schizophrenia

The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model attributing symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have...

) and psychomotor retardation sometimes seen in clinical depression

Clinical depression

Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

.