Social memory maintenance relies on social interaction-induced proteolytic products of neuroligin 1.

ABSTRACT: Proper social behaviors are essential for survival and success, and deficits in these behaviors are associated with many brain disorders. However, the mechanisms underlying the formation and maintenance of social memory remain poorly understood. In this study, we demonstrate that social interaction with unfamiliar mouse induces α- and γ-secretase-dependent proteolysis of Neuroligin 1 (NLG1) in the ventral hippocampus (vHPC). The intracellular hydrolysate fragment, NLG1-CTD, regulates synaptic plasticity, spine strengthening, and the maintenance of social memory through its PDZ binding domain (PBD) and the cofilin signaling pathway. Both γ-secretase inhibition and deletion of the secretase recognition site on NLG1 prevent cofilin phosphorylation and impair the maintenance of social memory b

SUBMITTER: Liu A 

PROVIDER: S-EPMC12641031 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature