Grant: CIHR Fellowship

Brain circuits are patterned by complex repertoires of neuronal cell-surface receptors which instruct each neuron to form precise patterns of connectivity and function. How do the immense diversity of neurons in the brain assemble from cues encoded by a limited number of genes? Two hints exist in literature. First, neural receptors in the central nervous system are subject to extraordinary expansion by alternative splicing and promotor/UTR usage, generating an expanded diversity of receptor isoforms at the transcriptional or post-transcriptional level. Second, combinatorial expression of receptor repertoires additionally confers near limitless numbers of receptor 'identities'. Despite their importance as central orchestrators of cell-cell communication, the receptor expression logic which underly developmental pathways remains largely unknown. A major challenge is the lack of tools to comprehensively study receptor expression and function in native brain tissue with cell-type, positional, sub-cellular, and splice variant information. Here, leveraging the unique intersection and synergy of new technologies developed by my postdoctoral labs, I aim to build a multimodal, spatially resolved developmental atlas of neuronal cell-surface receptor expression and function by simultaneously profiling, within single cells: 1) expression pattern for thousands of neural surface receptors in situ to ask if a neuron's receptor 'identity' changes during critical periods of development; and 2) long-term in vivo activity recordings to correlate transitions in activity patterns to receptor and channel expression at the global, cell-type and single neuron level. Together, this work will translate to the first atlas of surface receptor expression and function in the developing brain. With knowledge on how neural receptors are tuned for specific populations and functions, this work will advance ways to link molecular profiles of neurodevelopmental disorders with functional signatures.