substantia nigra

Definition: The substantia nigra is a brain structure located in the mesencephalon (midbrain) 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 dopaminergic neurons.

The substantia nigra is part of the basal ganglia; the other parts of the basal ganglia include the striatum (caudate nucleus and putamen), nucleus accumbens, and subthalamic nucleus.

Although the substantia nigra appears as a continuous band in brain sections, anatomical studies have found that it actually consists of two parts with very different connections and functions, the pars compacta and pars reticulata.

 The pars compacta serves mainly as an input to the basal ganglia circuit, supplying the striatum with dopamine.

 The pars reticulata, on the other hand, serves mainly as an output, conveying signals from the basal ganglia to numerous other brain structures.

Pathology

 Parkinson disease

Parkinson disease is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Parkinson disease is a neurodegenerative disease caused by the death of dopaminergic neurons in the pars compacta of the substantia nigra.

The major symptoms of Parkinson’s disease include tremor, akinesia, bradykinesia, and stiffness. Other symptoms include disturbances to posture, fatigue, sleep abnormalities, and depression.

The cause of death of dopaminergic neurons in the pars compacta is unknown. However, some contributions to the unique susceptibility of dopaminergic neurons in the pars compacta have been identified.

For one, dopaminergic neurons show abnormalities in mitochondrial complex 1, causing aggregation of alpha-synuclein (SNA). This could result in abnormal protein handling and neuron death.

Secondly, dopaminergic neurons in the pars compacta contain less calbindin than other dopaminergic neurons. Calbindin is a protein involved in calcium ion transport within cells, and excess calcium in cells is toxic.

The calbindin theory would explain the high cytotoxicity of Parkinson’s in the substantia nigra compared to the ventral tegmental area. Regardless of the cause of neuronal death, the plasticity of the pars compacta is very robust; Parkinsonian symptoms do not appear until up to 50-80% of pars compacta dopaminergic neurons have died.

Most of this plasticity occurs at the neurochemical level; dopamine transport systems are slowed, allowing dopamine to linger for longer periods of time in the chemical synapses in the striatum.

 s chizophrenia

According to the ’dopamine hypothesis of schizophrenia’, increased levels of dopamine have long been implicated in the development of schizophrenia.

However, much debate continues to this day surrounding this theory, commonly known as the dopamine hypothesis of schizophrenia. Despite the controversy, dopamine antagonists remain a standard and successful treatment for schizophrenia. These antagonists include first generation (typical) antipsychotics such as butyrophenones, phenothiazines, and thioxanthenes.

These drugs have largely been replaced by second generation (atypical) antipsychotics such as clozapine and paliperidone. It should be noted that these drugs generally do not act on dopamine-producing neurons themselves, but on the dopaminergic receptors on which the dopaminergic neurons synapse.

Other, non-pharmacological evidence in support of the dopamine hypothesis relating to the substantia nigra include structural changes in the pars compacta, such as reduction in synaptic terminal size.

Other changes in the substantia nigra include increased expression of NMDA receptors in the substantia nigra, and reduced dysbindin expression. Increased NMDA receptors may point to the involvement of glutamate-dopamine interactions in schizophrenia.

Dysbindin, which has been (controversially) linked to schizophrenia, may regulate dopamine release, and low expression of dysbindin in the substantia nigra may be important in schizophrenia etiology.

Due to the changes to the substantia nigra in the schizophrenic brain, it may eventually be possible to use specific imaging techniques (such as melanin-specific imaging) to detect physiological signs of schizophrenia in the substantia nigra.

See also

 brainstem