Assembly and plasticity of inhibitory cortical networks by early learning experience

The extraordinary diversity of animal behaviors relies on the precise assembly and fine-tuning of synapses in neuronal circuits that adapt to an ever-changing environment. Hence, mature networks are the final expression of experiences accumulated throughout our life. Importantly, young brains are more amenable to learning that older brains, but the neural mechanisms underlying these differences remain largely unknown. In the cerebral cortex, for example, there are two main classes of neurons, excitatory projection neurons (pyramidal cells) and inhibitory neurons (interneurons). Interneurons have a remarkable capability to sense changes in sensory experience and therefore occupy a unique position to orchestrate circuit remodeling. The goal of this project is to understand the mechanisms through which enhanced sensory experience during development sculpts cortical circuitries to improve behavioral performance in mice. To this end, we will use: (1) a synaptic connectivity mapping strategy (e-GRASP) and an activity-dependent promoter to explore specific cell- and synaptic-specific reorganizations driven by sensory experience; (2) sensory discrimination tasks and two-photon microscopy to explore the emergence of cortical functional properties, cell ensembles and behavioral performance; (3) unbiased screenings in cell populations and specific synapses together with single-cell RNA sequencing to identify genes that regulate cell-type specific modifications; and (4) loss of function approaches (shRNA and CRISPR/Cas9) to analyze the role of the identified candidate genes. Our research will shed light on the mechanisms shaping the assembly and function of cortical circuitries during early sensory experience.