Acute hyperexcitability differentially affects hippocampal neurogenesis features and spatial memory
Abstract
Introduction: Epileptic seizures induce aberrant adult hippocampal neurogenesis (AHN), yet how varying seizure intensities affect this process and associated memory functions remains unclear.
Methods: Here we administered systemically a low (5 mg/kg) or a high (25 mg/kg) dose of kainic acid (KA) to induce acute hyperexcitability of differing severity in mice of both sexes (6 to 8 weeks-old) genetically labeled for Ascl1, which allowed to follow progenitor cells and their progeny in the dentate gyrus (DG). We recorded EEG, assessed spatial and contextual fear memory, and analyzed adult-born granule cells (abGCs) 32 days post-treatment.
Results: High-dose KA produced more severe and prolonged seizures, increased mature abGCs with altered laminar positioning, and elevated dendritic spine density, whereas low-dose KA induced presynaptic bouton enlargement. Both doses impaired spatial location recognition but spared contextual fear memory.
Discussion: These findings reveal that acute seizure severity differentially modulates morphological and synaptic features of abGCs and selectively disrupts hippocampal-dependent spatial memory, indicating that hyperexcitability exerts qualitative effects on neurogenesis and cognitive function.
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