Bridging cellular and systems neuroscience: synaptic dynamics underlying behavior

连接细胞和系统神经科学：行为背后的突触动力学

• 批准号: 10261731
• 负责人: Michael James Higley
• 金额: $ 117.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10261731
• 关键词: Adaptive Behaviors; Animals; Area; Behavior; Behavioral; Brain; Communities; Data; Goals; Laboratories; Learning; Methodology; Modification; Molecular; Monitor; Mus; Neocortex; Nervous System Physiology; Nervous system structure; Neurons; Neurosciences; Perceptual learning; Probability; Process; Property; Synapses; Synaptic Transmission; Synaptic plasticity; System; Time; Variant; Visual Cortex; adaptive learning; base; in vivo; innovation; insight; synaptic function; visual motor

SUMMARY A major challenge to our progress in understanding the functional organization of the nervous system is the practical schism between cellular/molecular and systems sub-fields within the broader neuroscience community. For example, synaptic transmission is the fundamental mechanism by which activity propagates between neurons. While we have a detailed understanding of the cellular and molecular mechanisms underlying this process, the dynamic range and operating regime of synapses in the intact, behaving animal is essentially unknown. Based on recent data from our laboratory, our overall goal in this proposal is to investigate the hypothesis that variations in behavior over multiple time scales are associated with fluctuations in the strength of synaptic transmission within neuronal networks of the mammalian neocortex. With a groundbreaking combination of conceptual and methodological innovations, we will specifically identify the modifications of synaptic function that correspond to changes in behavioral state and perceptual learning. Specifically, we propose to monitor variation in synaptic release probability, potency, and integration for targeted circuits within the mouse visual cortex, relating these properties to behavioral state transitions and enhanced perceptual ability associated with visuomotor learning. Overall, this ambitious paradigm will generate critical new insights into the relationships between synapses, circuits, and behavior and open up new avenues of exploration that unite diverse areas of the neuroscience community.

总结 我们在理解神经系统功能组织方面的一个主要挑战是 在更广泛的神经科学中，细胞/分子和系统子领域之间的实际分裂 社区例如，突触传递是活动传播的基本机制 神经元之间。虽然我们对潜在的细胞和分子机制有了详细的了解， 这个过程，在完整的，行为动物的突触的动态范围和操作制度，基本上是 未知根据我们实验室的最新数据，我们在本提案中的总体目标是调查 假设在多个时间尺度上的行为变化与强度的波动有关 哺乳动物新皮层神经元网络内的突触传递。一个开创性的 结合概念和方法的创新，我们将具体确定修改 与行为状态和感知学习变化相对应的突触功能。我们特别 建议监测突触释放概率，效力和目标电路内的整合的变化 小鼠视觉皮层，将这些特性与行为状态转换和增强的感知能力联系起来 与视觉学习有关。总的来说，这一雄心勃勃的范式将产生关键的新见解， 突触、回路和行为之间的关系，并开辟了新的探索途径， 神经科学界的不同领域。