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。绘制哺乳动物大脑中神经元的连接图一直是神经科学中一个长期而重要的目标，因为更清楚地了解大脑区域之间和大脑区域内的通信将是揭示新的大脑功能的关键，例如形成和获得复杂动作。哺乳动物具有非凡的学习能力，并在高度控制下始终如一地执行各种动作。初级运动皮质已被证明可以产生自主运动并存储与运动相关的记忆，从而使人们能够学习新的运动模式。为了了解运动皮质如何产生和获得新的运动，人们进行了大量的研究工作。尽管关于运动技能学习过程中运动皮质内神经网络动力学的大量知识已经被探索，但运动皮质与哪些区域和哪些神经元交流的根本问题仍然难以捉摸。因此，了解具有细胞类型特异性的运动系统的基本解剖和功能接线图，对于提高我们对运动和运动学习的皮质机制的理解是至关重要的一步。*我们的实验室先前已经证明，运动学习导致锥体神经元抑制的差异性重塑，这是由运动皮质中不同数量的局部抑制性中间神经元介导的。因此，了解不同类型的抑制性神经元是否接受来自不同大脑区域的输入是很有趣的。在这个提案中，我们将集中在抑制性中间神经元的一个特定亚型，血管活性肠肽表达中间神经元(VIP-INS)。我们将使用新开发的单突触狂犬病病毒追踪方法，结合Cre重组酶策略，无偏见地将全脑输入映射到运动皮质中的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性。这项建议的结果将为了解未知的联系提供见解，这些联系在运动技能学习中可能很重要。同样的方法也可以用来理解运动皮质中其他抑制性神经元亚型的连通性，以帮助我们充分剖析大脑运动系统的复杂线路图。

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.