Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
Division of Health Management, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
ASN Neuro. 2023 Jan-Dec;15:17590914231206657. doi: 10.1177/17590914231206657.
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::InsR, GAD2::InsR) or glutamatergic neurons (vesicular glutamate transporter 2::InsR,Vglut2::InsR). Our results showed that in comparison to the InsR mice, both episodic and spatial memory were lower in GAD2::InsR and Vglut2::InsR. In addition, both GAD2::InsR and Vglut2::InsR 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.
众所周知，海马体是大脑中一个至关重要的区域，在情景和空间记忆中起着关键作用。胰岛素受体（InsRs）在海马体中分布密集，对其功能很重要。然而，InsRs 对特定海马体细胞类型功能的影响仍不清楚。在这项研究中，海马体 InsRs 敲除小鼠表现出情景和空间记忆受损。海马体中的 GABA 能神经元和谷氨酸能神经元参与兴奋性和抑制性（E/I）状态的平衡，并参与情景和空间记忆的过程。InsRs 主要位于海马体的兴奋性神经元中，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，我们构建了一种转基因小鼠系统，其中 InsR 表达从 GABA 能神经元（谷氨酸脱羧酶 2::InsR，GAD2::InsR）或谷氨酸能神经元（囊泡谷氨酸转运体 2::InsR，Vglut2::InsR）中缺失。我们的结果表明，与 InsR 小鼠相比，GAD2::InsR 和 Vglut2::InsR 小鼠的情景和空间记忆都较低。此外，GAD2::InsR 和 Vglut2::InsR 小鼠都表现出更多的焦虑和较低的葡萄糖耐量。这些发现表明，海马体 InsRs 可能通过调节海马体的 E/I 平衡对情景和空间记忆至关重要。
