GENE EXPRESSION PATTERNS OF SPATIAL MEMORY ENGRAMS IN MOUSE HIPPOCAMPUS

Memories in the brain are represented by engrams - groups of interconnected cells that are activated by a learning experience and necessary for recall of this experience. Most studies have focused on hippocampal fear memory engrams, but the hippocampus is especially important for spatial learning. Gene expression is required for memory formation, and distinct gene expression patterns may underlie different types of memory. Therefore, we aim to validate spatial excitatory and inhibitory engrams and identify any unique genetic signatures. Preliminary high-definition spatial sequencing experiments in mice that had undergone encoding and recall of a spatial memory in the radial 8-arm maze (RAM) revealed distinct expression patterns of immediate early genes following learning. We observe the presence of distinct populations of inhibitory cell types expressing immediate early genes confirmed by immmunohistochemistry and plan to compare the gene expression patterns of excitatory and inhibitory neuronal populations. To validate spatial engrams, TRAP2 mice injected in the hippocampus with an AAV-ArchT-tdT construct were trained on the RAM during which active cells were tagged. Preliminary experiments showed impaired memory when these tagged cells were optogenetically inhibited by 594nm light during recall. Following verification of spatial engrams we aim to use a combination of single cell and high-definition spatial transcriptomics to identify genetic signatures in tagged engram and non-engram cells. These experiments will reveal gene expression signatures specific to spatial memory.