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。

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10242872
• 关键词: Abstinence; Anatomy; Architecture; Aversive Stimulus; Award; Axon; Behavioral; Brain; Calcium; Cells; Cocaine; Cocaine Dependence; Complex; Cues; Data; Dendrites; Drug Addiction; Drug abuse; Electron Microscopy; Electrophysiology (science); Environment; Female; Fiber; Fiber Optics; GABA Receptor; Gender; Glutamate Receptor; Glutamates; Goals; Grant; Habenula; Human; Image; Immunoelectron Microscopy; Individual Differences; Intervention; Label; Lateral; Lead; Location; Measures; Mental Depression; Mental disorders; Mentors; Mentorship; Modeling; Morale; Mus; Neurons; Outcome; Pathway interactions; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Phase; Photometry; Play; Preoptic Areas; Presynaptic Terminals; Procedures; Process; Public Health; Publishing; Punishment; Research; Rewards; Role; Running; Self Administration; Sick Role; Signal Transduction; Stimulus; Structure; Sucrose; Synapses; Syndrome; Techniques; Testing; Tracer; Training; United States; Viral; Work; addiction; animal tissue; basal forebrain; calcium indicator; cocaine self-administration; conditioned fear; conditioned place preference; density; drug relapse; drug seeking behavior; dual diagnosis; experimental study; gamma-Aminobutyric Acid; gender difference; in vivo; in vivo calcium imaging; insight; interest; male; motivated behavior; nervous system disorder; neuronal cell body; novel; postsynaptic; preference; presynaptic; programs; receptor; response; reward processing; tool

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.

项目概要/摘要 药物成瘾是一种复杂的神经系统疾病，会导致边缘环路和神经系统功能异常。 边缘相关结构。基底前脑的一个特定部分——外侧视前区——充当 边缘结构和外侧缰核之间的重要中继，该区域与 在 Marisela Morales 和 Geoffrey Schoenbaum 博士的主要指导下， 目前的独立之路奖将使我能够获得电子显微镜和体内的培训 钙成像，以阐明视前缰核投影在处理 奖励和厌恶刺激，以及最终该电路在可卡因成瘾中所扮演的角色。 在这笔资助的指导阶段，我将结合使用病毒示踪剂和免疫电子显微镜 为了确定外侧视前区谷氨酸能和 GABA 能轴突的目标，从而建立 外侧缰核神经元上的突触并确定突触后受体的个体差异 随后，纤维 将使用光度测定钙成像来确定外侧视前神经末梢的情况 外侧缰核过程中的谷氨酸能和 GABA 能神经元奖励或厌恶结果以及 在独立阶段，我会将这些尖端技术与我之前的技术结合起来。 训练以同时记录外侧视前神经元的轴突末端 使用光纤光度法测量缰核，以及使用纤维光度法测量外侧缰核突触后细胞的反应 单单位电生理记录，以确定前视缰通路的作用 可卡因自我管理、惩罚性戒断和提示性恢复 总而言之， 独立之路奖中提出的研究将阐明超微结构和 参与可卡因自我管理的新型电路的功能机制，同时 为我提供了建立能够产生高影响力的独立研究项目的工具 将解剖数据与检查电路功能的尖端技术联系起来的研究。

项目成果

pMAT: An open-source software suite for the analysis of fiber photometry data.

pMAT：用于分析光纤光度测量数据的开源软件套件。

• 发表时间: 2021-02
• 作者: Bruno, Carissa A;O'Brien, Chris;Bryant, Svetlana;Mejaes, Jennifer I;Estrin, David J;Pizzano, Carina;Barker, David J
• 通讯作者: Barker, David J

Evaluating the in vivo glial response to miniaturized parylene cortical probes coated with an ultra-fast degrading polymer to aid insertion.

评估体内神经胶质细胞对涂有超快降解聚合物以帮助插入的微型聚对二甲苯皮层探针的反应。

• 发表时间: 2018
• 作者: Lo, Meng;Wang, Shuwu;Singh, Sagar;Damodaran, Vinod B;Ahmed, Ijaz;Coffey, Kevin;Barker, David;Saste, Kshitij;Kals, Karanvir;Kaplan, Hilton M;Kohn, Joachim;Shreiber, David I;Zahn, Jeffrey D
• 通讯作者: Zahn, Jeffrey D

Lateral preoptic area glutamate neurons relay nociceptive information to the ventral tegmental area.

外侧视前区谷氨酸神经元将伤害性信息传递至腹侧被盖区。

• 发表时间: 2023-09-26
• 影响因子: 8.8
• 作者: Barker, David J;Zhang, Shiliang;Wang, Huiling;Estrin, David J;Miranda;Liu, Bing;Kulkarni, Rucha J;de Deus, Junia Lara;Morales, Marisela
• 通讯作者: Morales, Marisela