Substantia nigra

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for 'black substance', reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. It was discovered in 1784 by Félix Vicq-d'Azyr, and Samuel Thomas von Sömmerring alluded to this structure in 1791. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. 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 (SNpc) and the pars reticulata (SNpr). This classification was first proposed by Sano in 1910. The pars compacta serves mainly as an output to the basal ganglia circuit, supplying the striatum with dopamine. The pars reticulata, though, serves mainly as an input, conveying signals from the basal ganglia to numerous other brain structures. The substantia nigra, along with four other nuclei, is part of the basal ganglia. It is the largest nucleus in the midbrain, lying dorsal to the cerebral peduncles. Humans have two substantiae nigrae, one on each side of the midline. The SN is divided into two parts: the pars reticulata (SNpr) and the pars compacta (SNpc), which lies medial to the pars reticulata. Sometimes, a third region, the pars lateralis, is mentioned, though it is usually classified as part of the pars reticulata. The (SNpr) and the internal globus pallidus (GPi) are separated by the internal capsule. The pars reticulata bears a strong structural and functional resemblance to the internal part of the globus pallidus. The two are sometimes considered parts of the same structure, separated by the white matter of the internal capsule. Like those of the globus pallidus, the neurons in pars reticulata are mainly GABAergic. The main input to the SNpr derives from the striatum. It comes by two routes, known as the direct and indirect pathways. The direct pathway consists of axons from medium spiny cells in the striatum that project directly to pars reticulata. The indirect pathway consists of three links: a projection from striatal medium spiny cells to the external part of the globus pallidus; a GABAergic projection from the globus pallidus to the subthalamic nucleus, and a glutamatergic projection from the subthalamic nucleus to the pars reticulata. Thus, striatal activity via the direct pathway exerts an inhibitory effect on neurons in the (SNpr) but an excitatory effect via the indirect pathway. The direct and indirect pathways originate from different subsets of striatal medium spiny cells: They are tightly intermingled, but express different types of dopamine receptors, as well as showing other neurochemical differences. Significant projections occur to the thalamus (ventral lateral and ventral anterior nuclei), superior colliculus, and other caudal nuclei from the pars reticulata (the nigrothalamic pathway), which use GABA as their neurotransmitter. In addition, these neurons form up to five collaterals that branch within both the pars compacta and pars reticulata, likely modulating dopaminergic activity in the pars compacta. The substantia nigra is an important player in brain function, in particular, in eye movement, motor planning, reward-seeking, learning, and addiction. Many of the substantia nigra's effects are mediated through the striatum. The nigral dopaminergic input to the striatum via the nigrostriatal pathway is intimately linked with the striatum's function. The co-dependence between the striatum and substantia nigra can be seen in this way: when the substantia nigra is electrically stimulated, no movement occurs; however, the symptoms of nigral degeneration due to Parkinson's is a poignant example of the substantia nigra's influence on movement. In addition to striatum-mediated functions, the substantia nigra also serves as a major source of GABAergic inhibition to various brain targets.