Dissecting the inhibitory architecture governing basal ganglia output

National Institute Of Neurological Disorders And Stroke

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Abstract

This year we have made excellent progress on our scientific goals. We developed a functional map of four genetically and anatomically defined inhibitory inputs onto the dopamine neurons of the substantia nigra pars compacta (SNc). We found that the striosome and matrix compartments of the striatum and the parvalbumin and lhx6 subpopulations of the globus pallidus differ in their impact on dopamine neuron activity. Specifically, striosomes selectively activate the ventrally-projecting SNr dendrite of SNc dopamine neurons. While a dendritic location suggests weak inhibitory control over a cell, we found that the striosomes effectively pause firing and hyperpolarized the cell. We found this to be due to both GABA-A and GABA-B receptor activation on the SNc dopamine neuron dendrites. This input strongly induced activity upon termination of the inhibition. Together these findings delineate a specific striatonigral circuit for inducing dopamine neuron rebound activity. Because these dopamine neurons inhibited by the striosomes project back to the striatum, this circuit represents a way for the striatum to control the timing of phasic dopamine signals back onto itself. Our work was submitted and published during this fiscal year (Evans et al. Cell Report 2020). In addition to this work, we co-authored paper with collaborator Huaibin Cai that reviewed Aldh1a1-positive neurons in the substantia nigra pars compacta.