Interaction of Glutamatergic Inputs to Nucleus Accumbens

谷氨酸能输入与伏隔核的相互作用

• 批准号: 9978349
• 负责人: Yan Dong
• 金额: $ 23.48万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978349
• 关键词: Address; Amygdaloid structure; Anatomy; Arousal; Automobile Driving; Aversive Stimulus; Behavior; Behavioral; Brain region; Cognition; Color; Cues; Dendrites; Dendritic Spines; Dopamine D1 Receptor; Dopamine D2 Receptor; Electrophysiology (science); Emotional; Foundations; Future; Glutamates; Hypothalamic structure; Individual; Knowledge; Label; Lasers; Mediating; Mental Depression; Motivation; Neurons; Nucleus Accumbens; Outcome; Output; Pattern; Physiological; Presynaptic Terminals; Rewards; Rhodopsin; Role; Slice; Solid; Structure; Structure of paraventricular nucleus of thalamus; Synapses; Synaptic Transmission; System; Techniques; Testing; Thalamic structure; Visceral; base; experimental study; hindbrain; insight; motivated behavior; nerve supply; postsynaptic; short-term potentiation; transmission process

Abstract The nucleus accumbens shell (NAcSh) receives glutamatergic projections from several limbic and paralimbic brain regions, with each projection presumably conveying different aspects of emotional and motivational arousals. In motivated behaviors, these excitatory inputs are typically activated concurrently, sending converging excitatory inputs to medium spiny neurons (MSNs), principal neurons in the NAcSh. While recent techniques allow for dissecting individual NAcSh projections, it remains largely unknown whether different NAcSh projections interact with each other when co-activated, and, if so, what the anatomical basis underlies these interactions. To start to address these knowledge gaps, this R21 application focuses on two prominent glutamatergic inputs to the NAcSh, the projections from the basolateral amygdala (BLAp) and paraventricular nucleus of the thalamus (PVTp). Both BLAp and PVTp form monosynaptic contacts onto NAcSh MSNs, but they are differentially involved in NAcSh-based behaviors. With the dual-rhodopsin expression system controlled by tow lasers with different wavelengths, we can simultaneously and independently activate BLAp and PVTp synaptic transmission to the same MSNs. The preliminary results show that a brief co-activation of these two projections induced a short-term potentiation in BLAp transmission but a short-term depression in PVTp transmission. Thus, co-activation temporarily boosted the informational flow through the BLAp while constrained the informational flow through the PCTp. These results not only indicate a clear functional interaction between the BLAp and PVTp, but also provide a potential circuit mechanism through which some motivational arousals override others under certain conditions. The first objective of this application is to extend these preliminary findings by exploring how BLAp and PVTp synapses functionally interact with each other on NAcSh MSNs. Using the dual-color SynapTag technique combined with postsynaptic filling, the second objective of this application is to determine the anatomical arrangement of the BLAp and PVTp that confers the functional interaction of these two projections. Outcomes of the proposed experiments may provide essential functional and anatomical mechanisms through which different aspects of emotional and motivational arousals interact and coordinate for behavioral prioritization.

抽象的 伏隔核壳（NACSH）接收来自几个边缘和paralimbic 大脑区域，每个投影大概传达了情感和激励的不同方面 唤醒。在动机行为中，这些兴奋性输入通常会同时激活，发送 将兴奋性输入转化为中刺神经元（MSN），NACSH中的主要神经元。最近 技术允许剖析单个NACSH的预测，在很大程度上尚不清楚是否不同 Nacsh投影在共激活时相互作用，如果是的，则解剖基础是什么 这些相互作用。为了解决这些知识差距，此R21应用程序重点关注两个突出的 NACSH的谷氨酸能输入，基底外侧杏仁核（Blap）和室室的投影 丘脑的核（PVTP）。 Blap和PVTP均形成单突触的接触，但 他们在基于NACSH的行为中有所不同。与双 - 偶像蛋白表达系统 由具有不同波长的拖曳激光器控制，我们可以同时且独立地激活Blap PVTP突触传输到同一MSN。初步结果表明，短暂的共同激活 这两个预测引起了空白传播的短期增强，但短期抑郁症 PVTP传输。因此，共同激活暂时增加了通过大声的信息流 限制了通过PCTP的信息流。这些结果不仅表明了清晰的功能 Blap和PVTP之间的相互作用，但也提供了潜在的电路机制 动机唤醒在某些条件下覆盖了他人。该应用程序的第一个目标是 通过探索BLAP和PVTP突触如何与每个功能相互作用，扩展这些初步发现 其他在NACSH MSN上。使用双色突触技术与突触后填充结合， 该应用的第二个目标是确定BLAP和PVTP的解剖学排列 赋予这两个预测的功能相互作用。提议的实验的结果可能 提供基本功能和解剖机制，通过这些机制，情感和情感的不同方面 动机唤醒相互作用并协调行为优先级。