Lesion of the perforant path triggers a biphasic neurogenic response in the adult dentate gyrus

The adult dentate gyrus exhibits dynamic remodeling through neurodegeneration and neurogenesis, particularly after injury. Using perforant path lesioning, we examined structural and functional plasticity in mature and newborn granule cells. Lesioning triggered marked proliferation and outward migration of newborn neurons, which formed dendritic spines even in denervated zones lacking excitatory terminals. Newborn neurons, but not mature cells, showed increased spine density in the inner molecular layer and enhanced miniature EPSC amplitudes. Laminar borders remained intact with layer-specific gliosis and extracellular matrix changes. These findings demonstrate injury-induced neurogenesis and synaptic reorganization, highlighting robust plasticity and adaptive circuit responses in the adult brain.