Electrophysiological Analysis of Serotonergic Afferent Regulation of Subpopulations of DA Neurons

Grant Type
Grant Year
Institution Location
Institution Organization Name
Sinai Research Institute
Investigators Name
Chiodo, Louis, PhD

There continues to be a general consensus among the scientific community that dopamine neuronal systems within the brain are, at least in part, importantly involved in the expression of the major symptoms of Tourette Syndrome. This hypothesis is supported by the well established observation that blockade of dopamine receptors (with such drugs as haloperidol) is often clinically efficacious in treating patients with this disorder. However, other therapeutic drugs are known to work through different mechanisms. For example, the alpha-noradrenergic receptor agonist clonidine appears to exert its effects on DA systems via influences on serotonergic afferents which affect either the dopamine neurons directly or dopamine-sensitive cells in the dopamine terminals fields (such as the neostriatum). Due to the complex and indirect nature of the interactions involved in clonidine’s actions on DA cells, we have undertaken a series of studies designed to better understand the nature of the serotonergic afferent regulation of the physiology and pharmacology of midbrain DA neurons. Previous work, supported by TSA, has shown that serotonergic afferents originating within the dorsal raphe nucleus have a profound influence on the activity of dopamine neurons which project to the head of the caudate nucleus. However, these influences are not uniform across all of these cells, but rather are restricted to about one-half of the population, particularly the dopamine neurons which have a lower spontaneous firing rate. These observations raise the possibility that this subpopulation of dopamine neurons fires slowly because they are under the direct influence of inhibitory serotonergic inputs. The present series of studies will examine the degree to which this observation is applicable to other subgroups of dopamine neurons such as slow- and fast-firing cells which project to the nucleus accumbens, prefrontal cortex and central nucleus of the amygdala. The results of these studies will provide important additional details about the physiology of identified subpopulations of dopamine neurons and the pharmacological actions of serotonergic agonists upon these same cells. Louis A. Chiodo, Ph.D. Sinai Research Institute, Detroit, MI Award $21,950 Tourette Association of America Inc. – Research Grant Award 1990