Synaptic Targeting in Hard-Wired Neural Circuits

硬连线神经回路中的突触靶向

• 批准号: RGPIN-2019-05849
• 负责人: Chen, Brian
• 金额: $ 2.33万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684446
• 关键词: Synaptic; Targeting; Hard; Wired; Neural

****** What are the molecular instructions to hard-wire precise synaptic connections? Only the most critical behaviours for survival are hard-wired into the genome. Behaviours such as breathing and primitive reflexes are not learned, and so the neural circuitry that controls them must be pre-specified using precise molecular instructions. Currently, we know very little about how hard-wired neural circuits are formed. The goal of my research is to identify every molecule necessary and sufficient to wire up a hard-wired neural circuit. My overall hypothesis is that a specific set of cell-surface molecules are required to generate a distinct hard-wired synaptic connectivity. My experimental approach will use single cell RNA sequencing of identified neurons in concert with a systematic characterization of all cell-surface receptors to understand how they can create the neuron's precise wiring pattern. We will then express these molecules in another neuron to re-wire its synaptic connections, alter its function, and thus alter the animal's perception and behavior. This research will be the first demonstration of the exact genetic instructions that can completely hardwire and mis-wire a neural circuit. By understanding how key molecules at the cell surface can produce erroneous synaptic connections, we can investigate ways to correct it. Our proposed work is an important first step towards understanding the molecular instructions underlying innate behaviours.

*硬连接精确突触连接的分子指令是什么？只有对生存最关键的行为才会固定在基因组中。诸如呼吸和原始反射之类的行为是无法学习的，因此控制它们的神经回路必须使用精确的分子指令预先指定。目前，我们对硬连线神经回路是如何形成的知之甚少。我的研究目标是确定每个必要和足够的分子来连接一个硬连线的神经电路。我的总体假设是，需要一组特定的细胞表面分子来产生独特的硬连接突触连接。我的实验方法将使用识别出的神经元的单细胞RNA测序，并结合所有细胞表面受体的系统特征，以了解它们如何创建神经元的精确连接模式。然后，我们将在另一个神经元中表达这些分子，以重新连接其突触连接，改变其功能，从而改变动物的感知和行为。这项研究将是第一次展示精确的遗传指令，它可以完全硬连接和错误连接神经电路。通过了解细胞表面的关键分子如何产生错误的突触连接，我们可以研究纠正它的方法。我们提出的工作是理解先天行为背后的分子指令的重要的第一步。