Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221004, Jiangsu, People's Republic of China.
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
J Neurosci. 2020 Sep 9;40(37):7119-7132. doi: 10.1523/JNEUROSCI.1121-20.2020. Epub 2020 Aug 6.
The nucleus accumbens shell (NAcSh) regulates emotional and motivational responses, a function mediated, in part, by integrating and prioritizing extensive glutamatergic projections from limbic and paralimbic brain regions. Each of these inputs is thought to encode unique aspects of emotional and motivational arousal. The projections do not operate alone, but rather are often activated simultaneously during motivated behaviors, during which they can interact and coordinate in shaping behavioral output. To understand the anatomic and physiological bases underlying these interprojection interactions, the current study in mice of both sexes focused on how the basolateral amygdala projection (BLAp) to the NAcSh regulates, and is regulated by, projections from the medial prefrontal cortex (mPFCp) and paraventricular nucleus of the thalamus (PVTp). Using a dual-color SynaptoTag technique combined with a backfilling spine imaging strategy, we found that all three afferent projections primarily targeted the secondary dendrites of NAcSh medium spiny neurons, forming putative synapses. We detected a low percentage of BLAp contacts closely adjacent to mPFCp or PVTp presumed synapses, and, on some rare occasions, the BLAp formed heterosynaptic interactions with mPFCp or PVTp profiles or appeared to contact the same spines. Using dual-rhodopsin optogenetics, we detected signs of dendritic summation of BLAp with PVTp and mPFCp inputs. Furthermore, high-frequency activation of BLAp synchronous with the PVTp or mPFCp resulted in a transient enhancement of the PVTp, but not mPFCp, transmission. These results provide anatomic and functional indices that the BLAp interacts with the mPFCp and PVTp for informational processing within the NAcSh. The nucleus accumbens regulates emotional and motivational responses by integrating extensive glutamatergic projections, but the anatomic and physiological bases on which these projections integrate and interact remain underexplored. Here, we used dual-color synaptic markers combined with backfilling of nucleus accumbens medium spiny neurons to reveal some unique anatomic alignments of presumed synapses from the basolateral amygdala, medial prefrontal cortex, and paraventricular nucleus of thalamus. We also used dual-rhodopsin optogenetics in brain slices, which reveal a nonlinear interaction between some, but not all, projections. These results provide compelling anatomic and physiological mechanisms through which different glutamatergic projections to the nucleus accumbens, and possibly different aspects of emotional and motivational arousal, interact with each other for final behavioral output.
伏隔核壳（NAcSh）调节情绪和动机反应，其功能部分通过整合和优先处理来自边缘和边缘旁脑区的广泛谷氨酸能投射来介导。这些输入中的每一个都被认为编码了情绪和动机唤醒的独特方面。这些投射并不是单独运作的，而是在动机行为期间通常同时被激活，在此期间，它们可以相互作用并协调，从而塑造行为输出。为了了解这些投射间相互作用的解剖学和生理学基础，本研究在雄性和雌性小鼠中重点研究了外侧杏仁核投射（BLAp）如何调节 NAcSh，并受来自内侧前额叶皮层（mPFCp）和丘脑室旁核（PVTp）的投射调节。使用双色 SynaptoTag 技术结合回溯 spine 成像策略，我们发现这三个传入投射主要靶向 NAcSh 中中型棘突神经元的二级树突，形成假定的突触。我们检测到 BLAp 与 mPFCp 或 PVTp 假定突触紧密相邻的接触的比例较低，并且在某些罕见情况下，BLAp 与 mPFCp 或 PVTp 形成异突触相互作用或似乎接触相同的棘突。使用双视紫红质光遗传学，我们检测到 BLAp 与 PVTp 和 mPFCp 输入的树突总和的迹象。此外，BLAp 的高频激活与 PVTp 或 mPFCp 同步，导致 PVTp 但不是 mPFCp 传递的短暂增强。这些结果提供了 BLAp 与 mPFCp 和 PVTp 相互作用进行 NAcSh 内信息处理的解剖学和功能指标。伏隔核通过整合广泛的谷氨酸能投射来调节情绪和动机反应，但这些投射整合和相互作用的解剖学和生理学基础仍未得到充分探索。在这里，我们使用双色突触标记物结合 NAcSh 中型棘突神经元的回溯，揭示了来自外侧杏仁核、内侧前额叶皮层和丘脑室旁核的假定突触的一些独特排列。我们还在脑片上使用双视紫红质光遗传学，这揭示了一些但不是所有投射之间的非线性相互作用。这些结果提供了引人注目的解剖学和生理学机制，通过这些机制，不同的谷氨酸能投射到伏隔核，以及情绪和动机唤醒的可能不同方面，相互作用以产生最终的行为输出。
