Disturbed engram network caused by NPTX downregulation underlies aging-related contextual fear memory deficits.

ABSTRACT: Engram cells storing episodic memories are allocated to separate neuronal ensembles. However, how these ensembles maintain their stability to drive precise memory expression, and whether their destabilization contributes to aging-related memory deficits, remain elusive. Here, we show that during contextual fear memory consolidation, neuronal pentraxin 1 (NPTX1) in Fos transcription-dependent ensemble (F-RAM) of the dentate gyrus (DG) promotes memory expression in the fear context. NPTX1 facilitates K_v7.2 channel-mediated inhibition of engram cell hyperexcitability, thereby restricting the response of these cells to excitatory inputs from medial entorhinal cortex. Meanwhile, NPTX2 enhances the perisomatic inhibition of Npas4 transcription-dependent ensemble (N-RAM) by parvalbumin

SUBMITTER: Jin T 

PROVIDER: S-EPMC12408839 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature