Subtype-Specific Connectivity of Local Inhibitory Interneurons in the Motor Cortex

大脑是一个由不同类型的神经元组成的网络，它们的连接为大脑中的信息流提供了框架。绘制哺乳动物大脑内的神经元连接是神经科学长期以来的一个重要目标，因为更清楚地了解大脑区域之间和内部的交流将是揭示大脑新功能（如复杂运动的形成和获得）的关键。哺乳动物拥有一种非凡的学习能力，能够在高度控制的情况下持续执行各种各样的动作。初级运动皮层已被证明可以产生自主运动并存储与运动相关的记忆，从而使新的运动模式得以学习。大量的研究工作旨在了解运动皮层如何使新运动的产生和获得成为可能。尽管在运动技能学习过程中，关于运动皮层内神经网络动力学的知识已经有了大量的探索，但运动皮层与哪些区域和哪些神经元通信的基本问题仍然是难以捉摸的。因此，了解运动系统的基本解剖和功能接线图，以及细胞类型特异性，是提高我们对运动运动和运动学习的皮层机制理解的重要一步。***我们的实验室先前已经证明，运动学习引起沿锥体神经元抑制的不同重塑，这是由运动皮层中不同的局部抑制性中间神经元群体介导的。因此，了解不同亚型的抑制性神经元是否接受来自不同大脑区域的输入是一个有趣的问题。在本研究中，我们将重点研究抑制性中间神经元的一个特定亚型，即血管活性肠肽表达中间神经元（VIP-INs）。我们将采用新开发的单突触狂犬病毒追踪方法，结合Cre-recombinase策略，无偏地将全脑输入映射到运动皮层的VIP-INs。我们还将使用体外和体内方法检查这些输入的功能连接。这项提议的结果将为运动技能学习中可能重要的未知连接提供见解。同样的方法可以应用于了解运动皮层中其他抑制性神经元亚型的连通性，以帮助我们全面剖析大脑中运动系统的复杂接线图。

The brain is a network that consists of diverse types of neurons and their connections provide the framework for information flow in the brain. Mapping neuronal connectivity within mammalian brains has been a long-standing and important goal in neuroscience because a clearer understanding of communication between and within brain regions will be key to uncovering the new brain functions such as formation and acquisition of complex movements. Mammals possess a remarkable ability to learn and consistently execute a wide range of movements with high levels of control. The primary motor cortex has been shown to produce voluntary movement and store movement-related memories, allowing new motor patterns to be learned. Considerable research efforts have been aimed at understanding how the motor cortex enables the generation and acquisition of new movements. Although a substantial body of knowledge pertaining to neural network dynamics within the motor cortex during motor skill learning has been explored, the fundamental question of which regions and which neurons the motor cortex communicates with remains elusive. Therefore, understanding the basic anatomical and functional wiring diagram of the motor system, with cell-type specificity, is an essential step in improving our understanding of the cortical mechanisms enabling motor movements and motor learning. ***Our lab has previously demonstrated that motor learning causes differential remodeling of inhibition along pyramidal neurons that is mediated by distinct populations of local inhibitory interneurons in the motor cortex. Hence, it is intriguing to understand whether different subtypes of inhibitory neurons receive inputs from different brain regions. In this proposal, we will focus on a specific subtype of inhibitory interneurons, the vasoactive intestinal peptide-expressing interneurons (VIP-INs). We will employ the newly developed monosynaptic rabies virus tracing method, combined with the Cre-recombinase strategy, to unbiasedly map brain-wide inputs to VIP-INs in the motor cortex. We will also examine the functional connectivity of these inputs using in vitro and in vivo approaches. Results from this proposal will provide insights to unknown connections that may be important in motor skill learning. The same methodologies can be applied to understand the connectivity of other inhibitory neuron subtypes in the motor cortex to help us to fully dissect the complex wiring diagram of the motor system in the brain.