Crossmodal plasticity in the auditory cortex in the precritical period - PROJECT SUMMARY Sensory experience facilitates structural and functional maturation of the developing nervous system, and sensory deprivation severely impairs them. Although the time course for experience-driven sensory development is specific for each modality, the developing brain acts as a whole. Therefore, sensory perturbation in one modality results in adaptive reorganization of neural pathways within the unaffected, spared modalities, a phenomenon known as “crossmodal plasticity.” Although a large body of literature has demonstrated adaptive crossmodal changes in the auditory cortex (ACtx) during the `classic critical period' (brief developmental period of enhanced sensory plasticity) after visual deprivation, it is, however, still not known how early in development crossmodal changes emerge. Based on recent findings that peripheral perturbations can alter ACtx circuits and function during the first two postnatal weeks of newborn mice (precritical period) and that crossmodal corticocortical connections are observed between the ACtx and visual cortex (VCtx), we hypothesized that complete retinal deprivation at birth results in crossmodal functional changes and circuit rearrangement in the ACtx and VCtx, during the precritical period. We will perform in vivo calcium imaging in unanesthetized mouse pups during the first two postnatal weeks before and soon after their ears and eyes are open (onset of the critical period) to assess crossmodal functional changes in the ACtx and VCtx following bilateral enucleation (complete retinal deprivation) at birth. We will also perform a combination of laser scanning photostimulation and in vitro whole cell patch clamp recording in slices as well as in vivo extracellular electrophysiology in unanesthetized pups to assess intra- and inter-cortical circuit changes following bilateral enucleation at birth. Results from the proposed experiments will provide, for the first time, functional evidence and a thorough assessment of crossmodal changes in the ACtx and VCtx during the precritical period as a result of complete retinal deprivation since birth and will provide a clear template to guide investigation of early crossmodal changes in other sensory pathways (e.g., somatosensory) and in other species during development. Moreover, the results will accentuate the impact of well-balanced ambient sensory environment in sensory development and will shed light on novel therapeutic interventions for the recovery of function of deprived senses in infants with sensory disorders, e.g., congenital hearing impairment.