Yu Wanting, Zhang Ruonan, Zhang Aohan, Mei Yufei
Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
Int J Mol Sci. 2025 Jan 30;26(3):1234. doi: 10.3390/ijms26031234.
Subcortical innervation of the hippocampus by the raphe nucleus is essential for emotional and cognitive control. The two major afferents from raphe to hippocampus originate from serotonergic and glutamatergic neurons, of which the serotonergic control of hippocampal inhibitory network, theta activity, and synaptic plasticity have been extensively explored in the growing body of literature, whereas those of glutamatergic circuits have received little attention. Notably, both serotonergic and glutamatergic circuits between raphe and hippocampus are disrupted in Alzheimer's disease (AD), which may contribute to initiation and progression of behavioral and psychological symptoms of dementia. Thus, deciphering the mechanism underlying abnormal raphe-hippocampal circuits in AD is crucial to prevent dementia-associated emotional and cognitive symptoms. In this review, we summarize the anatomical, neurochemical, and electrophysiological diversity of raphe nuclei as well as the architecture of raphe-hippocampal circuitry. We then elucidate subcortical control of hippocampal activity by raphe nuclei and their role in regulation of emotion and cognition. Additionally, we present an overview of disrupted raphe-hippocampal circuits in AD pathogenesis and analyze the available therapies that can potentially be used clinically to alleviate the neuropsychiatric symptoms and cognitive decline in AD course.
中缝核向海马体的皮质下神经支配对于情绪和认知控制至关重要。中缝核至海马体的两条主要传入神经源自血清素能神经元和谷氨酸能神经元，其中血清素能神经元对海马体抑制性网络、θ 活动及突触可塑性的控制已在大量文献中得到广泛探讨，而谷氨酸能神经回路的相关研究则较少受到关注。值得注意的是，中缝核与海马体之间的血清素能和谷氨酸能神经回路在阿尔茨海默病（AD）中均受到破坏，这可能导致痴呆的行为和心理症状的引发及进展。因此，解读 AD 中异常中缝核 - 海马体神经回路的潜在机制对于预防痴呆相关的情绪和认知症状至关重要。在本综述中，我们总结了中缝核的解剖学、神经化学和电生理学多样性以及中缝核 - 海马体神经回路的结构。然后我们阐明中缝核对海马体活动的皮质下控制及其在情绪和认知调节中的作用。此外，我们概述了 AD 发病机制中中缝核 - 海马体神经回路的破坏情况，并分析了可在临床上用于缓解 AD 病程中神经精神症状和认知衰退的现有治疗方法。
