Developmental emergence and age-related changes in the intra-cortical circuits of the auditory cortex

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Across the lifespan of an animal, there are two time periods- early development and aging- that produce radical alterations in the brain. While brain circuits become increasingly well-structured during early development (i.e., from perinatal days to the critical period), aging can lead to degenerative changes neural circuits. My study aims to investigate functional changes in primary auditory cortex (A1) across different development stages as well as aging and identify the cellular mechanisms behind these changes. First, I studied the development of intracortical connectivity in Layer 1 (L1) of mouse A1 and found a transient coupling between deep cortical layers, e.g., subplate neurons, to L1 neurons before and during the critical period. Since the normal development of cortical circuits can be affected by maternal exposure to drugs at an early age, I studied the impacts of perinatal opioid exposure on sound encoding and intra-cortical circuits in mouse A1 and observed persistent hypo-connectivity in excitatory circuits and reduced activity correlations. In addition to the perinatal period, the postnatal critical period also has a vital impact on the development of experience-driven plasticity in sensory cortices. To study the circuit changes induced by early activity manipulations, noise-reared animals are used, and the results showed degraded adaptation ability and persistent changes in intra-cortical circuits. The studies above focused on how early experience shapes the development of young brain circuits, while the aging process is also another period with significant brain plasticity. Thus, I performed circuit mapping experiments in L2/3 cells in two strains of mice, i.e., CBA/CaJ, which have normal hearing throughout their lives (normal aging), and C57/BL6J, which have early onset hearing loss (aged hearing loss). I found a sex-specific reduction in both excitatory and inhibitory intralaminar cortical circuits in aged mice and a specific reduction in excitatory and inhibitory intralaminar cortical circuits in aged hearing loss mice. Together, this dissertation combined in-vivo imaging techniques and different in-vitro patch clamp recording techniques to provide new insights into how early development and aging affect sound encoding and intra-cortical circuits under various scenarios.