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

Wenyu Ma; Tengxiao Si; Zan Wang; Pengjie Wen; Zhenxiang Zhu; Qing Liu; Jie Wang; Fuqiang Xu; Qin Li

doi:10.1016/j.celrep.2023.112674

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

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

Authors

Wenyu Ma¹, Tengxiao Si¹, Zan Wang¹, Pengjie Wen², Zhenxiang Zhu³, Qing Liu⁴, Jie Wang¹, Fuqiang Xu⁵, Qin Li⁶

Affiliations

¹ 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.
² 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.
³ 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; 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; University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ 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; University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ 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; 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; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: fq.xu@siat.ac.cn.
⁶ 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. Electronic address: liqin@apm.ac.cn.

PMID: 37352098
DOI: 10.1016/j.celrep.2023.112674

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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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.

Keywords: CP: Neuroscience; D-serine; LTP; TA-CA1 hippocampus; astrocyte; nicotine; synaptic plasticity; temporal association memory; α4-nAChRs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Astrocytes / metabolism
Hippocampus / metabolism
Long-Term Potentiation / physiology
Nicotine* / metabolism
Nicotine* / pharmacology
Nicotinic Agonists / metabolism
Receptors, Nicotinic* / metabolism

Substances

Nicotine
Nicotinic Agonists
Receptors, Nicotinic