Subpopulations of hippocampal inhibitory interneurons contribute differently to engram formation in APP/PS1 mice

Understanding the neural mechanisms underlying memory formation and retrieval is fundamental to unraveling the pathophysiology of Alzheimer's disease (AD). Inhibitory interneurons have fundamental roles in shaping neural circuits and synaptic plasticity within the hippocampus, a brain region critical for memory encoding and consolidation. However, the specific contribution of inhibitory interneurons to the formation and maintenance of engrams, the neural representations of memories, remains poorly understood, particularly in the context of AD.To determine neurons participating in the engram formation in regions CA1, CA3, and DG of the hippocampus, we targeted the immediate early gene FOS as a marker following exposure to environmental enrichment in comparison to standard housing conditions. This was done in combination with markers targeting specific interneuron subpopulations (SOM, PV, VIP, CCK) to assess their participation in engram formation both in the APP/PS1 mouse model of Alzheimer’s disease and matched controls.Our preliminary results obtained from immunohistochemistry stainings imaged through high-resolution confocal microscopy indicate that the number and ratio of each inhibitory interneuron subpopulation analyzed here vary according to the housing conditions and genotypes.These findings have significant implications for understanding the pathophysiology of memory impairments in AD and may provide insights into novel therapeutic strategies for alleviating cognitive decline in affected individuals. Furthermore, by elucidating the role of inhibitory interneurons in engram formation and function, this research contributes to advancing our understanding of memory processes and may ultimately lead to the development of targeted treatments for memory-related disorders.