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: $ 4.37万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746575
• 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信息流提供了框架。在哺乳动物大脑中绘制神经元连通性是神经科学的长期和重要目标，因为对大脑区域和大脑区域之间的交流有更清晰的了解将是揭示新的大脑功能（例如形成和复杂运动的获取）的关键。哺乳动物具有出色的学习能力，并持续执行具有高水平控制的运动。主要的运动皮层已被证明会产生自愿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。大量的研究工作旨在了解运动皮层如何使新运动产生和获取。尽管已经探索了运动技能学习过程中与运动皮层内神经网络动态有关的大量知识，但已经探索了运动皮层学习过程中的知识，但基本的问题是哪些区域以及运动皮层的神经元与哪些神经元与哪些神经元进行交流。因此，了解具有细胞类型特异性的电机系统的基本解剖和功能接线图，是提高我们对带动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，运动学习会导致沿锥体神经元抑制的差异重塑，这是由运动皮质中局部抑制性中间神经元不同种群介导的。因此，很有趣的是了解抑制性神经元的不同亚型是否从不同的大脑区域接收投入。在此提案中，我们将重点关注抑制性中间神经元的特定亚型，即表达表达肽的血管活性肠中神经元（VIP-INS）。我们将采用新开发的单突触狂犬病病毒追踪方法，再加上CRE聚集酶策略，以公正地将大脑范围的输入映射到运动皮层中的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。该提案的结果将为未知连接提供见解，这些联系在运动技能学习中可能很重要。可以应用相同的方法来了解运动皮层中其他抑制性神经元亚型的连通性，以帮助我们完全剖析大脑中电动机系统的复杂接线图。