Postnatal experience shapes gene expression and connectivity development in the cortex

项目总结

PROJECT SUMMARY Postnatal sensory experience has a profound effect on the maturation, composition, and connectivity of cortical cell types, but systematic analyses of these changes have not yet been feasible. This lack of methods for systematic analysis had made it difficult to define principles in how neural activity re-wires brain circuits and whether connectivity changes precede or follow molecular changes in brain cell types. Systematically characterizing how neural activity from the sensory periphery shapes the molecular and synaptic properties of neural circuits in the brain would benefit from new technologies in which synaptic connectivity relationships and genome-wide RNAs could be measured in vivo from the same individual cells. High-throughput, single-cell resolved methods to profile gene expression and synaptic connectivity – including the barcoded rabies virus- based method called Slide-SBARRO method developed in the Saunders Lab - are well suited to study how sensory input influences cortical circuit formation. In Aim 1, I will use an inducible mouse model paired with single nucleus RNA sequencing of primary auditory cortex (A1) cells to determine how auditory input shapes cortical cell-type proportions and gene expression. In Aim 2, I will determine how auditory input shapes local synaptic relationships within A1 by reconstructing hundreds of spatially resolved and cell-type-specific monosynaptic networks using Slide-SBARRO. By comprehensively characterizing how auditory sensory input alters brain cell and circuit properties in A1, this proposal will enhance our understanding of the mechanisms through which cortex responds to damage in the sensory periphery. Finally, this proposal will allow me to develop new technical skills and intellectual approaches that I will use to study auditory circuit plasticity as an independent researcher.