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.

NARRATIVE Synaptic connections between neurons form the basis of network connectivity in the brain, and synaptic plasticity is widely believed to underlie adaptive behavior and learning. However, the dynamic range and modulation of synaptic strength in vivo is essentially unknown, raising a major challenge to our understanding of nervous system function. Here, we combine conceptual and methodological innovations to drive a pioneering exploration of the relationship between synaptic transmission and ongoing behavior.