The entire dopamine projection system arises from only a few thousand neurons located in the midbrain. One subgroup, the substantia nigra, innervates chiefly the caudate nucleus and putamen which lie in the basal ganglia — a brain region that controls movement. The substantia nigra also contains a non-dopamine neuron population by means of which it is brought into close relation to other sensory and motor brain regions. Degeneration of the dopamine neurons of the substantia nigra has been found to occur in Parkinson's disease, a condition characterized by poverty of movement (hypokinesia), tremor, and rigidity. It seems likely, then, that these symptoms are related to disturbance in the coordination of neural activity in these circuits. Several observations strongly suggest that in Parkinson's disease both the basal ganglia and thalamus are concerned with the appearance of tremor and rigidity. It is probable that the globus pallidus (a subregion of the basal ganglia) is more concerned with the production of rigidity, while the thalamus is concerned with tremor. Successful neurosurgical treatment of these symptoms can be achieved by destroying small areas of these parts of the brain. On the other hand, it seems that the hypokinesia of Parkinsonism is due to degeneration of dopaminergic neurons. Thus it seems that there is a distinction between those symptoms in the Parkinsonian syndrome which are due to dopamine, and those due to non-dopamine neurons. Indeed, symptoms of hypokinesia can occur independently of rigidity and tremor. Hypokinesia can be successfully treated by giving the patient levodopa, an amino acid that is taken up in the brain and converted to the neurotransmitter dopamine in those dopamine neurons not affected by the disease.
The other main dopamine subgroup of neurons innervates various nuclei in the limbic system, including the amygdala. They are likely to be closely involved in the organism's emotional response to the environment. The same dopamine group also provides an innervation to important areas of the cerebral cortex — the frontal and temporal lobe cortices. Both these areas (particularly the latter) are targets for convergence of association fibres from extremely wide expanses of neocortex. They therefore provide potential anatomical structures in which the highest of cortical functions can be carried out. In man they are likely to be involved in the functions of memory, intellect, and personality. Dopamine neurons innervating these cortical regions also receive inputs from hypothalamic areas and the basal forebrain. These regions appear to be closely involved in motivation, learning, and rewarding mechanisms. Schizophrenia is a condition which appears to be sensitive to the action of drugs that act on brain areas innervated by dopamine neurons. Drugs which act more selectively on only the limbic and cortical dopamine systems are also antipsychotic. Thus it may be that disturbance of these neurons, particularly those related to the amygdala and the temporal lobe cortex, may play an important part in the development of this condition.
(Published 1987)
— O. T. Phillipson
