Experience-dependent plasticity of circuit dynamics - PROJECT SUMMARY: Plasticity of neural circuits is a key element underlying the brain's ability to adapt to experience, and harnessing plasticity in the brain may provide new therapeutic avenues to ameliorate the effects of early perturbation or injury. However, our understanding of plasticity in the adult brain remains incomplete. Although adult plasticity in the visual cortex can be selectively induced through loss of sensory input or repeated presentation of single stimuli, the impact of more broadly enriched sensory experience is unclear. In addition, although the role of GABAergic inhibition in developmental visual plasticity has been deeply explored, the role of inhibitory interneurons in adult plasticity remains largely unknown. In particular, cells that express the peptide somatostatin (SST-INs) are thought to play a critical role in shaping the feature selectivity of visual responses in mouse visual cortex, primarily via their robust inhibition of the dendrites of excitatory pyramidal neurons. SST- INs are also critical mediators of visually-evoked activity patterns that facilitate long-range transmission of visual information. However, the functional roles of SST-INs in adult plasticity remain unclear. Our preliminary data suggest the surprising finding that visual experience consisting of repeated presentations of varied stimuli induces a novel form of plasticity in adult mouse primary visual cortex, leading to robust enhancement of visually evoked activity in SST-INs. This experience-dependent plasticity is accompanied by altered visual sensitivity in nearby excitatory neurons. To further explore this observation, we propose to combine a number of methodological approaches, including 2-photon imaging of identified neural populations, optogenetic manipulations, and ex vivo synaptic physiology. We will determine the visual experience required to induce this adult plasticity, identify the underlying cellular and synaptic mechanisms, and examine the functional consequences for cortical visual encoding and transmission. Our results will provide an unprecedented level of insight into a novel form of plasticity in the adult cortex and identify underlying cellular- and circuit-level mechanisms.
