GADD45B in the ventral hippocampal CA1 modulates aversive memory acquisition and spatial cognition.

Autor:	Huang M; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Tao X; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Bao J; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Wang J; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Gong X; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Luo L; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Pan S; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Yang R; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Gui Y; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Zhou H; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Xia Y; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Yang Y; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Sun B; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China., Liu W; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China. Electronic address: liuwei@jhun.edu.cn., Shu X; Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China. Electronic address: xijishu@jhun.edu.cn.
Jazyk:	angličtina
Zdroj:	Life sciences [Life Sci] 2024 Jun 01; Vol. 346, pp. 122618. Date of Electronic Publication: 2024 Apr 12.
DOI:	10.1016/j.lfs.2024.122618
Abstrakt:	Aims: This study was designed to investigate the role of growth arrest and DNA damage-inducible β (GADD45B) in modulating fear memory acquisition and elucidate its underlying mechanisms. Main Methods: Adeno-associated virus (AAV) that knockdown or overexpression GADD45B were injected into ventral hippocampal CA1 (vCA1) by stereotactic, and verified by fluorescence and Western blot. The contextual fear conditioning paradigm was employed to examine the involvement of GADD45B in modulating aversive memory acquisition. The Y-maze and novel location recognition (NLR) tests were used to examine non-aversive cognition. The synaptic plasticity and electrophysiological properties of neurons were measured by slice patch clamp. Key Findings: Knockdown of GADD45B in the vCA1 significantly enhanced fear memory acquisition, accompanied by an upregulation of long-term potentiation (LTP) expression and intrinsic excitability of vCA1 pyramidal neurons (PNs). Conversely, overexpression of GADD45B produced the opposite effects. Notably, silencing the activity of vCA1 neurons abolished the impact of GADD45B knockdown on fear memory development. Moreover, mice with vCA1 GADD45B overexpression exhibited impaired spatial cognition, whereas mice with GADD45B knockdown did not display such impairment. Significance: These results provided compelling evidence for the crucial involvement of GADD45B in the formation of aversive memory and spatial cognition. Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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