Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
Career Assistant Project, Hiroshima University, Higashi-Hiroshima, 739-8521, Japan.
Sci Rep. 2021 Jun 30;11(1):13589. doi: 10.1038/s41598-021-93045-7.
Social behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory. Alzheimer's disease (AD) is mainly characterized by progressive dementia and is accompanied by cognitive impairments, including a decline in social ability. The cholinergic system is a potential constituent for the neural mechanisms underlying social behaviour, and impaired social ability in AD may have a cholinergic basis. However, the involvement of cholinergic function in social behaviour has not yet been fully understood. Here, we performed a selective elimination of cholinergic cell groups in the basal forebrain in mice to examine the role of cholinergic function in social interaction and social recognition memory by using the three-chamber test. Elimination of cholinergic neurons in the medial septum (MS) and vertical diagonal band of Broca (vDB) caused impairment in social interaction, whereas ablating cholinergic neurons in the nucleus basalis magnocellularis (NBM) impaired social recognition memory. These impairments were restored by treatment with cholinesterase inhibitors, leading to cholinergic system activation. Our findings indicate distinct roles of MS/vDB and NBM cholinergic neurons in social interaction and social recognition memory, suggesting that cholinergic dysfunction may explain social ability deficits associated with AD symptoms.
社交行为是一个复杂的结构,据报道包括社交接近、互动和识别记忆等几个组成部分。阿尔茨海默病(AD)主要表现为进行性痴呆,并伴有认知障碍,包括社交能力下降。胆碱能系统是社交行为潜在的神经机制组成部分,AD 中受损的社交能力可能具有胆碱能基础。然而,胆碱能功能在社交行为中的作用尚未完全阐明。在这里,我们通过三箱测试在小鼠的基底前脑选择性消除胆碱能细胞群,以研究胆碱能功能在社交互动和社交识别记忆中的作用。中隔(MS)和 Broca 垂直对角带(vDB)中的胆碱能神经元的消除导致社交互动受损,而基底核大细胞(NBM)中的胆碱能神经元的消除则损害了社交识别记忆。这些损伤可以通过用胆碱酯酶抑制剂治疗来恢复,从而激活胆碱能系统。我们的发现表明 MS/vDB 和 NBM 胆碱能神经元在社交互动和社交识别记忆中具有不同的作用,这表明胆碱能功能障碍可能解释了与 AD 症状相关的社交能力缺陷。