Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load.

ABSTRACT: Working memory (WM) is a fundamental cognitive function crucial adaptive behavior. The intricate interplay between the frontal cortex and striatum in governing WM maintenance and updating remains a central question. In this study, we employed optogenetics to demonstrate that inhibiting both dorsomedial striatum (DMS) D1R- and D2R-neurons enhances WM, while their activation impairs it across T-maze and operant-based delayed-non-match-to-place (DNMTP) paradigms in mice. Notably, these neurons selectively modulate WM maintenance and retrieval, with no impact on encoding. Analysis through signal detection theory (SDT) revealed specific regulation of WM signal detection sensitivity, with no alterations in motivational or motor states during the operant DNMTP task. Interestingly, DMS D2R-neurons

SUBMITTER: Chen XJ 

PROVIDER: S-EPMC12310021 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature