Project Summary

Mahesh Thakkar, Ph.D. (Young Investigator 2004) of VA Boston Healthcare System Brockton/Harvard University, aims to study in cats the neurochemical control of monoaminergic neurons, lower activity of which is implicated in major depressive disorder. The experiments will focus on the control and the regulation of dorsal raphe neurons at the cellular/molecular level using a novel combination of microdialysis and extracellular unit recording in freely behaving cats. Dr. Thakkar hypothesizes that GABA, a major inhibitory neurotransmitter, may play a pivotal role in inhibiting monoaminergic neurons, particularly the serotonergic neurons of the dorsal raphe. The major hypothesis to be investigated is whether GABAergic input acting through the GABA-A receptor inhibits the discharge activity of dorsal raphe serotonergic neurons. Dr. Thakkar also will test the effects of GABAergic agonists/antagonist perfused in the dorsal raphe (increased or decreased serotonergic tone) on the extracellular release of GABA in three different regions of the brain including the hippocampus, prefrontal cortex and amygdala.

Program Area: MOOD DISORDERS\Mood Disorders (General)

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