EXPRESSION DYNAMICS OF CLUSTERED PROTOCADHERINS IN HIPPOCAMPAL ENGRAM CELLS

Memories are stored in neuronal ensembles known as engram cells through activity-dependent plasticity. During memory acquisition, engram cells are thought to refine their synaptic connectivity to support stable information storage, a process that relies on cell adhesion molecules mediating precise cell–cell interactions. Clustered protocadherins (cPcdhs), the largest subgroup of the cadherin superfamily with 57 genes in mice, function as molecular barcodes that enable highly specific neuronal recognition and are essential for neuronal self-avoidance during development. However, their expression patterns and potential roles in adult memory engrams remain poorly understood.
Here, we combined engram labelling with spatial transcriptomics and single-nucleus RNA sequencing to characterize cPcdhs expression in engram and non-engram hippocampal cells following memory encoding and recall. We generated a comprehensive map of cPcdh isoforms expression across hippocampal cell types and identified sparse, cell-type-specific cPcdh profiles. Importantly, we observed activity-associated changes in cPcdhs expression, revealing dynamic regulation of protocadherin profiles during memory processes. Together, these data provide a transcriptomic framework for understanding how cPcdhs may contribute to engram organization and memory-related circuit specificity.