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

运动皮层局部抑制性中间神经元的亚型特异性连接

• 批准号: RGPIN-2017-05308
• 负责人: Chen, Simon
• 金额: $ 2.19万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711606
• 关键词: Subtype; Specific; Connectivity; Local; Inhibitory

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.

大脑是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的神经元连接一直是神经科学的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内部的通信将是揭示新的大脑功能的关键，例如复杂运动的形成和获得。哺乳动物具有非凡的学习能力，并能在高度控制的情况下持续执行各种各样的动作。初级运动皮层已经被证明可以产生自主运动并存储与运动相关的记忆，从而可以学习新的运动模式。相当多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。虽然大量的知识涉及运动技能学习过程中运动皮层内的神经网络动力学已经被探索，运动皮层与哪些区域和哪些神经元通信的基本问题仍然难以捉摸。因此，了解运动系统的基本解剖学和功能布线图，以及细胞类型特异性，是提高我们对实现运动运动和运动学习的皮质机制的理解的重要步骤。 我们的实验室先前已经证明，运动学习导致抑制的差异重塑沿着锥体神经元，这是由运动皮层中的局部抑制性中间神经元的不同群体介导的。因此，理解不同亚型的抑制性神经元是否从不同的大脑区域接收输入是有趣的。在这个建议中，我们将集中在一个特定的亚型抑制性中间神经元，血管活性肠肽表达中间神经元（VIP-IN）。我们将采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研究这些输入的功能连接。从这个建议的结果将提供见解未知的连接，可能是重要的运动技能学习。同样的方法也可以用来理解运动皮层中其他抑制性神经元亚型的连接，以帮助我们全面剖析大脑中运动系统的复杂接线图。