Regulating brain development through sensorimotor experience-dependent neurogenesis

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Postembryonic development marks the period in life when sensory experience has its greatest impact on brain development. Experience-dependent changes in brain development are often assumed to occur via synaptic plasticity. However, the effects of sensory experience on other forms of neuroplasticity, such as neurogenesis, are largely unexplored. Understanding the capacity of the sensory environment to modulate neurogenesis is important because perturbations in developmental neurogenesis are thought to initiate aberrant neurodevelopmental trajectories that culminate in neuropsychiatric illness. Accordingly, the long-term goal of my research is to understand how sensory experience shapes brain development through the modulation of neurogenesis. Previously, I found that somatosensory feedback from the body during movement stimulates neurogenesis in the forebrain of zebrafish larvae. I believe this form of movement-dependent neurogenesis represents a fundamental form of sensorimotor feedback coupling motor and brain development early in life. The short-term goal of my research is to elucidate the mechanism through which motor experience modulates neurogenic brain development. I will achieve this goal by answering three questions: How does sensorimotor feedback reach the brain? Dorsal root ganglia (DRG), sensory cells in the body, convey feedback during movement to regulate forebrain neurogenesis. However, the pathway carrying DRG input to the brain is unknown. Using both anatomical mapping of isolated DRG neurites and functional mapping of neuronal activity evoked by DRG activation I will identify hindbrain nuclei that receive and process DRG ascending input. Upon reaching the hindbrain, how does sensorimotor feedback then reach the forebrain? DRG neurites terminate within the hindbrain where nuclei must then convey this ascending sensory input to regulate forebrain neurogenesis. I hypothesize that the locus coeruleus (LC), a noradrenergic hindbrain nucleus, mediates movement-dependent neurogenesis. Using transgenically modified zebrafish, in which LC can be ablated or optogenetically stimulated, I will test the importance of LC signaling in movement-dependent forebrain neurogenesis. How does motor experience modulate neurogenic development? Neurogenesis encapsulates processes including cell proliferation, fate, and survival, and how motor experience affects these different processes is unknown. Using intersectional transgenic approaches to isolate neural stem cell lineages in vivo and histologically, I will test how motor experience shapes the forebrain neurodevelopmental trajectory via the modulation of different neurogenic processes. Answering these questions will elucidate the neural circuitry through which ascending motor feedback affects early brain growth. This work will greatly expand our understanding of the importance of sensory experience in shaping the neurodevelopmental trajectory through the modulation of neurogenesis.