星形胶质细胞 5-HT1A 受体介导雄性小鼠年龄依赖性海马 LTD 和恐惧记忆的消退

IF 9.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Experimental and Molecular Medicine Pub Date : 2024-08-01 DOI:10.1038/s12276-024-01285-0
Qian-Yun Wu, Lian-Hong Lin, Kun Lu, Si-Fu Deng, Wei-Min Li, Yuan Xu, Bin Zhang, Ji-Hong Liu
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摘要

海马中的 NMDA 受体依赖性长期抑制(LTD)是一种众所周知的突触可塑性形式,与不同的认知功能有关。虽然其潜在机制尚不清楚,但这种形式的LTD在成年小鼠中无法通过低频刺激(LFS)诱导。在这项研究中,我们发现低频刺激诱导的LTD在成年动物中不易诱导,而且与年龄有关。有趣的是,在发育过程中,5-HT1A 受体的水平相应升高,并与 LFS-LTD 的程度呈反相关。敲除或药物抑制 5-HT1A 受体可逆转成年小鼠(P60)受损的 LFS-LTD,而激活或抑制该受体可分别干扰或增强青少年小鼠(P21)的 LFS-LTD。此外,海马中星形胶质细胞的5-HT1A受体主要通过增强GABA能神经递质介导年龄依赖性LFS-LTD。最后,恐惧记忆的消退在上述条件下有所不同。这些观察结果丰富了我们对细胞水平LTD的认识,并为LTD相关精神疾病的治疗提供了思路。
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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. Understanding how our brains learn and remember is intriguing. As we age, our learning and memory abilities can alter, and scientists are trying to understand why. A recent study investigates this by studying a specific brain receptor, the 5-HT1A receptor, and its effect on learning and memory in mice. The team focused on a process called long-term depression. They found that the ability to induce LTD changes with age and that the 5-HT1A receptor plays a key role in this. They discovered that the activity of 5-HT1A receptors in certain brain cells, astrocytes, is necessary for LTD and influences fear memory extinction. The researchers conclude that the 5-HT1A receptor in astrocytes plays a crucial role in regulating learning and memory processes related to LTD. This discovery could lead to new treatments for memory-related disorders. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
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来源期刊
Experimental and Molecular Medicine
Experimental and Molecular Medicine 医学-生化与分子生物学
CiteScore
19.50
自引率
0.80%
发文量
166
审稿时长
3 months
期刊介绍: Experimental & Molecular Medicine (EMM) stands as Korea's pioneering biochemistry journal, established in 1964 and rejuvenated in 1996 as an Open Access, fully peer-reviewed international journal. Dedicated to advancing translational research and showcasing recent breakthroughs in the biomedical realm, EMM invites submissions encompassing genetic, molecular, and cellular studies of human physiology and diseases. Emphasizing the correlation between experimental and translational research and enhanced clinical benefits, the journal actively encourages contributions employing specific molecular tools. Welcoming studies that bridge basic discoveries with clinical relevance, alongside articles demonstrating clear in vivo significance and novelty, Experimental & Molecular Medicine proudly serves as an open-access, online-only repository of cutting-edge medical research.
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