Project Summary/Abstract The brain undergoes extensive synaptic plasticity and circuit refinement during development. Similar changes recur throughout life during learning in a more narrowly constrained manner. Understanding how neuronal connections and activity are adaptively remodeled to accommodate a changing world remains an outstanding question in neuroscience research. Recent technological innovations provide unprecedented access to address this. Here, the proposal focuses on the circuit mechanisms that reconfigure neuronal ensembles in mouse primary visual cortex (V1) during development and learning. In response to visual demands, cortical ensembles shift their response properties to “give” salience to relevant features in visual space. Using volumetric two-photon (2P) microscopy, the candidate will longitudinally track the activity of thousands of neurons in V1, with single-cell resolution, throughout visual learning. The candidate will then use a spatial light modulator (SLM) to activate and inactivate specific functionally and/or molecularly defined subpopulations of neurons to causally uncover circuit elements that underlie cortical plasticity. Second, having mastered an “all-optical” approach to record and interrogate neurons, the candidate will study the role that a specific developmental activity period plays in establishing orientation tuning in cortical ensembles and probe how eliminating this computation alters visual perception. Successful completion of this project will provide new insights to the circuit mechanisms that establish homeostasis in neuronal activity while simultaneously yielding sufficient flexibility to accommodate learning. Many neuropathological states arise when this balance is disrupted. A greater understanding of physiological circuit function undoubtedly precedes, and will contribute to, the development of novel therapeutics to treat disorders of the nervous system. Finally, this work will position the candidate to establish an independent research program which interrogates how information from developmentally hardwired sensory circuits converges with malleable cortical ensembles to generate visually-guided behaviors.

Project Narrative Plasticity mechanisms reconfigure brain circuits to accommodate a changing world. Circuit reconfiguration is most profound during learning and development, but also in disease. This study will integrate novel tools and conceptual approaches to advance our understanding of the circuit dynamics of perception and cognition, establishing benchmarks for future development of therapeutics to treat disorders of the nervous system.