Dataset Information

Astrocytic 5-HT_1A receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.

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_1A 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_1A 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_1A 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.

SUBMITTER: Wu QY

PROVIDER: S-EPMC11371825 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Astrocytic 5-HT<sub>1A</sub> receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.

Wu Qian-Yun QY Lin Lian-Hong LH Lu Kun K Deng Si-Fu SF Li Wei-Min WM Xu Yuan Y Zhang Bin B Liu Ji-Hong JH

Experimental & molecular medicine 20240801 8

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<sub>1A</sub> receptor was correspondingly increase ...[more]

PMID: 39085354

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Project description:BackgroundPosttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity.MethodsFirst, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells.ResultsA single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC.ConclusionsA single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.

Dataset Information

Astrocytic 5-HT_1A receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.

Publications

Astrocytic 5-HT<sub>1A</sub> receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.

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Dataset Information

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

Publications

Astrocytic 5-HT<sub>1A</sub> receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Astrocytic 5-HT_1A receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.