Bridging cellular and systems neuroscience: synaptic dynamics underlying behavior

摘要 我们在了解神经系统功能组织方面取得进展的一个主要挑战是 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 在神经元之间。虽然我们对潜在的细胞和分子机制有详细的了解 这一过程，突触的动态范围和运作机制，在完整的，行为的动物基本上是 未知。根据我们实验室的最新数据，我们在这项建议中的总体目标是调查 假设行为在多个时间尺度上的变化与强度的波动有关 哺乳动物大脑皮层神经元网络中突触传递的研究。具有开创性的 结合概念和方法创新，我们将具体确定 与行为状态和知觉学习的变化相对应的突触功能。具体来说，我们 建议监测目标回路的突触释放概率、效力和整合的变化 小鼠的视觉皮质，将这些特性与行为状态转换和增强的感知能力联系起来 与视觉运动学习有关。总体而言，这一雄心勃勃的范例将产生对 突触、回路和行为之间的关系，并开辟了联合的新探索途径 神经科学界的不同领域。

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.