Dissecting the inhibitory architecture governing basal ganglia output

今年我在我的科学目标上取得了很好的进展。在这个项目中，我开发了四种基因和解剖学定义的抑制输入到黑质致密部（SNc）多巴胺神经元的功能图谱。我发现纹状体的纹状体和基质区室以及苍白球的小白蛋白和lhx6亚群对多巴胺神经元活动的影响是不同的。具体来说，纹状体选择性地激活SNc多巴胺神经元的腹侧突出的SNr树突。虽然树突位置表明对细胞的抑制控制较弱，但我们发现纹状体有效地暂停放电并使细胞超极化。我们发现这是由于GABA-A和GABA-B受体在SNc多巴胺神经元树突上的激活。当抑制被释放时，这种类型的输入强烈地诱导了活动的反弹。相比之下，来自苍白球的输入没有强烈的多巴胺神经元超极化，也没有诱导反弹活动。总之，这些发现描绘了一个特定的纹状体神经回路，以诱导多巴胺神经元的反弹活动。因为这些被纹状体抑制的多巴胺神经元投射回纹状体，这个回路代表了纹状体控制阶段性多巴胺信号传回自身的时间的一种方式。这些发现在今年的会议上受到了好评。我从海报摘要中被选中参加戈登儿茶酚胺研究研讨会的演讲，从那里，我被选为戈登儿茶酚胺研究会议的演讲。我还在巴塞罗那的计算神经科学组织（OCNS）会议上展示了这个项目，这个项目被选为年度NINDS撤退的海报奖。这个项目正在准备发表，我目前正在进行体内光遗传学实验来跟进这些发现。

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.