Developmental and Adult GAP-43 Deficiency in Mice Dynamically Alters Hippocampal Neurogenesis and Mossy Fiber Volume

Growth-associated protein-43 (GAP-43) is a presynaptic protein that plays key roles in axonal growth and guidance and in modulating synapse formation. Previous work has demonstrated that mice lacking one allele of this gene (GAP43+/– mice) exhibit hippocampal structural abnormalities, impaired spatial learning and stress-induced behavioral withdrawal and anxiety, behaviors that are dependent on proper hippocampal circuitry and function. Given the correlation between hippocampal function, synaptic connectivity and neurogenesis, we tested if behaviorally naive GAP43+/– mice had alterations in either neurogenesis or synaptic connectivity in the hippocampus during early postnatal development and young adulthood, and following behavior testing in older adults. To test our hypothesis, we examined hippocampal cell proliferation (Ki67), number of immature neuroblasts (doublecortin, DCX) and mossy fiber volume (synaptoporin) in behaviorally naive postnatal day 9 (P9)