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: 10217090
• 负责人: Yan Dong
• 金额: $ 19.59万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217090
• 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) 接收来自多个边缘系统和旁边缘系统的谷氨酸能投射 大脑区域，每个投影大概传达情感和动机的不同方面 唤醒。在动机行为中，这些兴奋性输入通常同时激活，发送 将兴奋性输入汇聚到中型棘神经元 (MSN)，即 NAcSh 中的主要神经元。虽然最近 技术允许剖析单独的 NAcSh 投影，但仍然很大程度上未知是否不同 NAcSh 投射在共同激活时会相互作用，如果是的话，其解剖学基础是什么 这些相互作用。为了开始解决这些知识差距，此 R21 应用程序重点关注两个突出的问题 NAcSh 的谷氨酸输入、基底外侧杏仁核 (BLAp) 和室旁的投射 丘脑核 (PVTp)。 BLAp 和 PVTp 都在 NAcSh MSN 上形成单突触接触，但是 他们不同程度地参与基于 NAcSh 的行为。采用双视紫红质表达系统 由两束不同波长的激光器控制，我们可以同时独立地激活BLAp 和 PVTp 突触传输到相同的 MSN。初步结果表明，短暂的共激活 这两个预测导致了 BLAp 传播的短期增强，但导致了 BLAp 传播的短期抑制。 PVTp传输。因此，共激活暂时增强了通过 BLAp 的信息流，同时 限制了通过 PCTp 的信息流。这些结果不仅表明了明确的功能 BLAp 和 PVTp 之间的相互作用，还提供了一种潜在的电路机制，通过该机制，一些 在某些条件下，动机的激发会凌驾于其他动机之上。该应用程序的第一个目标是 通过探索 BLAp 和 PVTp 突触如何在功能上相互作用来扩展这些初步发现 NAcSh MSN 上的其他内容。使用双色 SynapTag 技术结合突触后填充， 该应用的第二个目标是确定 BLAp 和 PVTp 的解剖结构， 赋予这两个投影的功能相互作用。拟议实验的结果可能 提供基本的功能和解剖机制，通过这些机制，情绪和情绪的不同方面 动机唤醒相互作用并协调行为优先顺序。