Nigrostriatal neuronal pathway

Nigrostriatal tract The major dopaminergic neuronal pathway linking midbrain and forebrain basal ganglia. 

Figure 30-12 Diagram illustrating some of the major interconnections of the "extrapyramidal system" of the brain. Arrows indicate major direction of projections. The nigrostriatal (substantia nigra to striatum) and related neuronal pathways are indicated with dashed lines. After Nohack and Demarest,405 pp. 182 and 183.

FIGURE 11-5. Long-term blockade of dopamine 2 receptors by dopamine 2 antagonists in the nigrostriatal dopamine pathway may cause these receptors to up-regulate. A clinical consequence of this may be the hyperkinetic movement disorder known as tardive dyskinesia. This up regulation may be the consequence of the neuron s futile attempt to overcome drug-induced blockade of its dopamine receptors. 

FIGURE 11-9. Dopamine and acetylcholine have a reciprocal relationship in the nigrostriatal dopamine pathway. Dopamine neurons here make postsynaptic connections with cholinergic neurons. Normally, dopamine suppresses acetylcholine activity. 

FIGURE 11-22. Now dopamine (DA) release is being inhibited by serotonin (5HT) in the nigrostriatal dopamine pathway. When serotonin occupies its 5HT2A receptor on the dopamine neuron (lower red circle), this inhibits dopamine release, so there is no dopamine in the synapse (upper red circle). Compare this with Figure 11—21. 

The nigrostriatal tract is one of the four main dopaminergic pathways in the central nervous system. About 75% of the dopamine in the brain occurs in the nigrostriatal pathway with its cell bodies in the substantia nigra, whose axons project in the corpus striatum. Degeneration of the dopaminergic neurons in the nigrostriatal system results in Parkinsons disease. 

As with many neurons (e.g. NA) there are presynaptic autoreceptors on the terminals of dopamine neurons whose activation attenuate DA release. Although most of these receptors appear to be of the D2 type, as found postsynaptically, D3 receptors are also found. It is possible that in addition to the short-term control of transmitter release they may also be linked directly to the control of the synthesising enzyme tyrosine hydroxylase. It seems that autoreceptors are more common on the terminals of nerves in the nigrostriatal (and possibly mesolimbic) than mesocortical pathway. 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

Unlike many chemicals in the brain, neurotransmitters are not homogeneously distributed, but concentrated in certain regions. For example, almost two-thirds of the dopamine in the brain is found in the bilateral nigrostriatal (mesostriatal) tract (pathway), where the neuronal cell bodies are located in the substantia nigra and the axons terminate in the corpus striatum. When over 85% of these dopaminergic neurons are lost, the characteristic motor dysfunction of Parkinson s disease is seen. 

Parkinson s disease (shaking palsy) and its syndromal forms are caused by a degeneration of nigrostriatal dopamine neurons. The resulting striatal dopamine deficiency leads to overactivity of choUnergic intemeurons and imbalance of striopallidal output pathways, manifested by poverty of movement (akinesia), muscle stiffness (rigidity), tremor at rest, postural instability, and gait disturbance. 

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