Astrocytic 5-HT Receptor Mediates Age-dependent Hippocampal LTD and Fear Memory Extinction in Male Mice

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2024 Jul 31

PMID 39085354

Authors

Qian-Yun Wu

Lian-Hong Lin

Kun Lu

Si-Fu Deng

Wei-Min Li

Yuan Xu

Bin Zhang

Ji-Hong Liu

Affiliations

Soon will be listed here.

Abstract

NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. Although the underlying mechanisms remain unclear, this form of LTD cannot be induced by low-frequency stimulation (LFS) in adult mice. In this study, we found that LFS-induced LTD was not easily induced in adult animals and was age dependent. Interestingly, the level of the 5-HT receptor was correspondingly increased and exhibited an inverse correlation with the magnitude of LFS-LTD during development. Knockout or pharmacological inhibition of the 5-HT receptor reversed impaired LFS-LTD in adult mice (P60), while activation or inhibition of this receptor disturbed or enhanced LFS-LTD in adolescent mice (P21), respectively. Furthermore, the astrocytic 5-HT receptor in the hippocampus predominantly mediated age-dependent LFS-LTD through enhancing GABAergic neurotransmission. Finally, fear memory extinction differed among the above conditions. These observations enrich our knowledge of LTD at the cellular level and suggest a therapeutic approach for LTD-related psychiatric disorders.

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