权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Defining the differential roles of Glutamatergic and GABAergic projections from the Lateral Preoptic Area to the Lateral Habenula in Reward, Aversion, and Drug-Seeking Behavior.

定义从外侧视前区到外侧缰核的谷氨酸能和 GABA 能投射在奖励、厌恶和药物寻求行为中的不同作用。

基本信息

批准号：
10242872
负责人：
David J Barker
金额：
$ 24.9万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2023-08-31
项目状态：
已结题

项目摘要

Project Summary/Abstract Drug addiction is a complex neurological disorder which produces aberrant function in limbic circuits and limbic-associated structures. One specific portion of the basal forebrain—the lateral preoptic area—serves as an important relay between limbic structures and the lateral habenula, a region that has been implicated in addiction and depression. Under the primary mentorship of Drs. Marisela Morales and Geoffrey Schoenbaum, the present Pathway to Independence award will allow me to obtain training in electron microscopy and in vivo calcium imaging in order to elucidate the role of the preopto-habenular projection in the processing of rewarding and aversive stimuli, and eventually the role that this circuitry plays in cocaine addiction. In the mentored phase of this grant, I will use a combination of viral tracers and immuno-electron microscopy in order to determine the targets of the lateral preoptic area glutamatergic and GABAergic axons that establish synapses on lateral habenula neurons and to determine how individual differences in postsynaptic receptors contribute to individual differences in the processing of rewarding and aversive stimuli. Subsequently, fiber photometry calcium imaging will be used in order to determine how the terminals of lateral preoptic glutamatergic and GABAergic neurons in the lateral habenula process rewarding or aversive outcomes and their associated cues. In the independent phase, I will combine these cutting-edge techniques with my prior training in order to simultaneously record the axon terminals of lateral preoptic neurons in the lateral habenula using fiber photometry and the responses of the postsynaptic cells in the lateral habenula using single-unit electrophysiological recordings in order to establish a role for the preopto-habenular pathway in cocaine self-administration, punishment-imposed abstinence, and cued reinstatement. In summary, the research proposed in this Pathway to Independence Award will elucidate the ultrastructural architecture and functional mechanisms of a novel circuit that participates in cocaine self-administration while simultaneously providing me with the tools to establish an independent research program capable of producing high impact studies that bridge anatomical data with cutting-edge techniques for examining circuit function.

项目摘要/摘要药物成瘾是一种复杂的神经疾病，它会导致边缘回路和边缘相关结构。基底前脑的一个特定部分--外侧视前区--起着边缘结构和外侧缰核之间的重要联系，这一区域已被牵连到上瘾和抑郁。在玛丽塞拉·莫拉莱斯博士和杰弗里·舍恩鲍姆博士的主要指导下，目前的独立之路奖将使我获得电子显微镜和活体方面的培训钙显象以阐明视前缰核投射在脑发育过程中的作用奖赏和厌恶刺激，以及最终这个回路在可卡因成瘾中所起的作用。在在这笔赠款的指导阶段，我将结合使用病毒示踪剂和免疫电子显微镜确定视前外侧区谷氨酸和氨基丁酸能轴突的靶点外侧缰核神经元上的突触和确定突触后受体的个体差异在奖赏和厌恶刺激的加工过程中，个体的差异起到了一定的作用。随后，光纤将用光度法钙成像来确定视前外侧的终末如何外侧缰核中的谷氨酸和GABA能神经元奖赏或厌恶结果和它们的相关线索。在独立阶段，我将把这些尖端技术与我之前的训练以同时记录外侧视前神经元的轴突终末缰核纤维光度测定法和外侧缰核突触后细胞对纤维光度的反应单单位电生理记录以确定视-缰核前通路在脑内的作用可卡因自我管理，惩罚禁欲，并暗示复职。总而言之，在这一独立之路奖中提出的研究将阐明超微结构和一种同时参与可卡因自我给药的新回路的作用机制为我提供了建立能够产生高影响力的独立研究计划的工具研究将解剖学数据与检查电路功能的尖端技术相结合。