This year I have made excellent progress on my scientific goals. For this project, I developed a functional map of four genetically and anatomically defined inhibitory inputs onto the dopamine neurons of the substantia nigra pars compacta (SNc). I 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 type of input strongly induces a rebound in activity when the inhibition is released. By contrast, the inputs from the globus pallidus did not strongly hyperpolarize the dopamine neurons and did not induce rebound activity. 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. These findings have been well-received at conferences this year. I was selected from the poster abstracts for a talk at the Catecholamines Gordon Research Seminar and, from there, was selected as a talk for the Catecholamines Gordon Research Conference. I also presented this project at the organization for computational neuroscience (OCNS) conference in Barcelona and this project was selected for a poster prize at the annual NINDS retreat. This project is being prepared for publication and I am currently following up these findings with in vivo optogenetic experiments. I have also made good progress in my career goals this year, receiving the BRAIN Initiative K99/R00 pathway to independence award and publishing a co-authored paper with collaborator Huaibin Cai. In addition, I have taken advantage of several training programs offered by NIH including sessions in the workplace dynamics series, the seminar on applying for academic faculty positions, and a hands-on data visualization workshop.
