Astrocytic 5-HT1A receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.

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-HT1A receptor was correspondingly increased and exhibited an inverse correlation with the magnitude of LFS-LTD during development. Knockout or pharmacological inhibition of the 5-HT1A 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-HT1A 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. © 2024. The Author(s).

Citation

Qian-Yun Wu, Lian-Hong Lin, Kun Lu, Si-Fu Deng, Wei-Min Li, Yuan Xu, Bin Zhang, Ji-Hong Liu. Astrocytic 5-HT1A receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice. Experimental & molecular medicine. 2024 Aug;56(8):1763-1775

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PMID: 39085354

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