海马星形细胞 α4 包含型烟碱型乙酰胆碱受体信号调控着时间关联记忆的形成。

Astrocytic α4-containing nAChR signaling in the hippocampus governs the formation of temporal association memory.

机构信息

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Shenzhen Key Laboratory of Viral Vectors for Biomedicine, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

出版信息

Cell Rep. 2023 Jul 25;42(7):112674. doi: 10.1016/j.celrep.2023.112674. Epub 2023 Jun 22.

DOI:10.1016/j.celrep.2023.112674

PMID:37352098

Abstract

Everyday episodic memories involve linking together related events that are temporally separated. However, the mechanisms of forming this temporal association have remained unclear. Here, using astrocyte-specific manipulations, we show that potentiating astrocyte Ca signaling in the hippocampal cornu ammonis 1 (CA1) enhances the strength of such temporal association, in parallel with long-term potentiation (LTP) enhancement of temporoammonic pathway to CA1, whereas attenuation of astrocyte Ca signaling has the opposite effect. Moreover, we identify that these effects are mediated by astrocytic α4 subunit-containing nicotinic acetylcholine receptors (α4-nAChRs) via mechanisms involving NMDAR co-agonist supply. Finally, astrocytic α4-nAChRs underlie the cognitive enhancer nicotine's physiological effects. Together, these findings highlight the importance of astrocyte Ca signaling in cognitive behavior and reveal a mechanism in governing the temporal association of episodic memory formation that operates through α4-nAChRs on hippocampal astrocytes.

摘要

每日情景记忆涉及将时间上分离的相关事件联系在一起。然而，形成这种时间关联的机制仍不清楚。在这里，我们使用星形胶质细胞特异性操作，表明在海马角 1（CA1）中增强星形胶质细胞 Ca 信号会增强这种时间关联的强度，与 temporoammonic 途径到 CA1 的长时程增强（LTP）增强平行，而减弱星形胶质细胞 Ca 信号则产生相反的效果。此外，我们确定这些效应是通过星形胶质细胞 α4 亚基包含的烟碱型乙酰胆碱受体（α4-nAChR）介导的，其机制涉及 NMDAR 共激动剂供应。最后，星形胶质细胞 α4-nAChR 是尼古丁生理效应的认知增强剂的基础。总之，这些发现强调了星形胶质细胞 Ca 信号在认知行为中的重要性，并揭示了一种通过海马星形胶质细胞上的 α4-nAChR 来调节情景记忆形成的时间关联的机制。