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/摘要吸毒成瘾是一种复杂的神经系统疾病，在边缘电路中产生异常功能边缘相关结构。基本前脑的一个特定部分 - 侧面前区域 - 作为一个边缘结构与外侧Habenula之间的重要继电器，该地区已在成瘾和抑郁。在博士的主要心态下。 Marisela Morales和Geoffrey Schoenbaum，目前的独立奖项将使我能够获得电子显微镜和体内的培训钙成像是为了阐明前距离投影在加工中的作用奖励和厌恶刺激，最终是该电路在可卡因成瘾中所扮演的作用。在该赠款的鉴定阶段，我将使用病毒示踪剂和免疫电子显微镜的组合为了确定建立的侧向前区域谷氨酸能和GABA能的靶标在侧habenula神经元上的突触，并确定突触后受体的个体差异在奖励和厌恶刺激的处理过程中有助于个体差异。随后，纤维光度法钙成像将用于确定横向前的末端如何在外侧Habenula过程中，谷氨酸能和GABA能神经元有益或厌恶结果他们相关的提示。在独立阶段，我将将这些尖端技术与我的先前结合在一起训练以简单地记录侧面前神经元的轴突端子使用纤维光度法和外侧Habenula中突触后细胞的反应的Habenula使用单单元电生理记录，以确立前晋升途径的作用可卡因自我管理，受到惩罚的禁欲和提示恢复原状。总而言之，在这项获得独立奖励奖励的研究将阐明超微结构建筑和同时参与可卡因自我管理的新型电路的功能机制为我提供工具，以建立能够产生高影响力的独立研究计划研究启动解剖学数据的研究，以检查电路功能的尖端技术。