Interaction of Glutamatergic Inputs to Nucleus Accumbens

摘要 中脑核壳（NAcSh）接受来自多个边缘系统和中脑边缘系统的神经元投射 大脑区域，每个投射可能传达不同方面的情绪和动机， 唤醒在动机行为中，这些兴奋性输入通常同时激活， 将兴奋性输入汇聚到中等多刺神经元（MSN），NAcSh中的主要神经元。虽然最近 技术允许解剖单个NAcSh投影，但在很大程度上仍然不清楚是否不同 当共同激活时，NAcSh投射相互作用，如果是这样，解剖学基础是什么？ 这些互动。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 NAcSh的突触能输入，来自基底外侧杏仁核（BLAp）和室旁核的投射， 丘脑核（PVTp）。BLAp和PVTp都与NAcSh MSN形成单突触接触，但 它们在基于NAcSH的行为中有差异。双视紫红质表达系统 通过两种不同波长的激光控制，我们可以同时独立地激活BLAp， 和PVTp突触传递到相同的MSN。初步结果表明， 这两种投射在BLAp传递中引起短期增强，但在BLAp传递中引起短期抑制。 PVTp传输。因此，共激活暂时促进了通过BLAp的信息流， 限制了信息通过PCTp的流动。这些结果不仅表明了一个明确的功能 BLAp和PVTp之间的相互作用，而且还提供了一种潜在的电路机制，通过这种机制， 在某些条件下，动机性唤醒会凌驾于其他唤醒之上。本申请的第一个目的是 通过探索BLAp和PVTp突触如何在功能上相互作用， 另一个是NAcSh MSN。使用双色SynapTag技术结合突触后填充， 本申请的第二个目的是确定BLAp和PVTp的解剖学排列， 赋予了这两个投影的功能性相互作用。拟议实验的结果可能 提供了重要的功能和解剖机制，通过这些机制， 动机唤醒相互作用并协调行为优先级。

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.