Dissecting the inhibitory architecture governing basal ganglia output

今年，我在我的科学目标上取得了出色的进步。在这个项目中，我绘制了一张功能图，其中包括四个从基因和解剖学上定义的对黑质致密部(SNC)多巴胺神经元的抑制输入。我发现纹状体的纹状体和基质隔区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。具体地说，纹状体选择性地激活黑质多巴胺神经元的腹侧投射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了激活并使细胞超极化。我们发现这是由于黑质多巴胺神经元树突上GABA-A和GABA-B受体的激活。当抑制被释放时，这种类型的输入强烈地诱导活性反弹。相比之下，来自苍白球的输入并没有强烈地使多巴胺神经元超极化，也没有引起反弹活动。总而言之，这些发现描绘了诱导多巴胺神经元反弹活动的特定纹状体黑质回路。因为这些被纹状体抑制的多巴胺神经元投射回纹状体，所以这个回路代表了纹状体控制多巴胺信号时相返回自身的一种方式。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为儿茶酚胺戈登研究研讨会的演讲对象，并从那里被选为儿茶酚胺戈登研究会议的演讲对象。我还在巴塞罗那举行的计算神经科学组织(OCNs)会议上介绍了这个项目，该项目被选为NINDS年度静修活动的海报奖。这个项目正在准备发表，我目前正在用活体光遗传学实验来跟进这些发现。 今年，我的职业目标也取得了很好的进步，获得了大脑倡议K99/R00独立之路奖，并与合作者蔡怀斌共同发表了一篇论文。此外，我还利用了美国国立卫生研究院提供的几个培训项目，包括工作场所动态系列课程、学术教师职位申请研讨会和实际操作数据可视化研讨会。

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.