Hippocampus Insulin Receptors Regulate Episodic and Spatial Memory Through Excitatory/Inhibitory Balance.

IF 3.9 4区 医学 Q2 NEUROSCIENCES ASN NEURO Pub Date : 2023-01-01 DOI:10.1177/17590914231206657
Cai-Yan Xue, Tian Gao, E Mao, Zhen-Zhen Kou, Ling Dong, Feng Gao
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Abstract

It is well known that the hippocampus is a vital brain region playing a key role in both episodic and spatial memory. Insulin receptors (InsRs) are densely distributed in the hippocampus and are important for its function. However, the effects of InsRs on the function of the specific hippocampal cell types remain elusive. In this study, hippocampal InsRs knockout mice had impaired episodic and spatial memory. GABAergic neurons and glutamatergic neurons in the hippocampus are involved in the balance between excitatory and inhibitory (E/I) states and participate in the processes of episodic and spatial memory. InsRs are located mainly at excitatory neurons in the hippocampus, whereas 8.5% of InsRs are glutamic acid decarboxylase 2 (GAD2)::Ai9-positive (GABAergic) neurons. Next, we constructed a transgenic mouse system in which InsR expression was deleted from GABAergic (glutamate decarboxylase 2::InsRfl/fl, GAD2Cre::InsRfl/fl) or glutamatergic neurons (vesicular glutamate transporter 2::InsRfl/fl,Vglut2Cre::InsRfl/fl). Our results showed that in comparison to the InsRfl/fl mice, both episodic and spatial memory were lower in GAD2Cre::InsRfl/fl and Vglut2Cre::InsRfl/fl. In addition, both GAD2Cre::InsRfl/fl and Vglut2Cre::InsRfl/fl were associated with more anxiety and lower glucose tolerance. These findings reveal that hippocampal InsRs might be crucial for episodic and spatial memory through E/I balance hippocampal regulation.

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海马胰岛素受体通过兴奋/抑制平衡调节情景和空间记忆。
众所周知,海马体是大脑中至关重要的区域,在情景记忆和空间记忆中都发挥着关键作用。胰岛素受体(InsRs)密集分布在海马体中,对其功能很重要。然而,InsRs对特定海马细胞类型功能的影响仍然难以捉摸。在这项研究中,海马InsRs敲除小鼠的情景记忆和空间记忆受损。海马中的GABA能神经元和谷氨酸能神经元参与兴奋和抑制(E/I)状态之间的平衡,并参与情景记忆和空间记忆的过程。InsRs主要位于海马的兴奋性神经元,而8.5%的InsRs是谷氨酸脱羧酶2(GAD2)::Ai9阳性(GABA能)神经元。接下来,我们构建了一个转基因小鼠系统,其中InsR表达从GABA能神经元(谷氨酸脱羧酶2::InsRfl/fl,GAD2Cr::InsRfl/fl)或谷氨酸能神经元(囊泡谷氨酸转运体2::InsRfl/fl,Vglut2Cr::InsRfl/fl)中缺失。我们的研究结果表明,与InsRfl/fl小鼠相比,GAD2Cr::InsRfl/fl和Vglut2Cr::Insirfl/fl小鼠的情景记忆和空间记忆都较低。此外,GAD2Cr::InsRfl/fl和Vglut2Cr::Insirfl/fl都与更多的焦虑和更低的糖耐量有关。这些发现表明,海马InsRs可能通过E/I平衡海马调节对情景记忆和空间记忆至关重要。
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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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