Schmitz Taylor W, Zaborszky Laszlo
Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, United States.
Handb Clin Neurol. 2021;179:159-173. doi: 10.1016/B978-0-12-819975-6.00008-X.
The basal forebrain (BF) cholinergic system constitutes a heterogeneous cluster of large projection neurons that innervate the entire cortical mantle and amygdala. Cholinergic neuromodulation plays a critical role in regulating cognition and behavior, as well as maintenance of cellular homeostasis. Decades of postmortem histology research have demonstrated that the BF cholinergic neurons are selectively vulnerable to aging and age-related neuropathology in degenerative diseases such as Alzheimer's and Parkinson's diseases. Emerging evidence from in vivo neuroimaging research, which permits longitudinal tracking of at-risk individuals, indicates that cholinergic neurodegeneration might play an earlier and more pivotal role in these diseases than was previously appreciated. Despite these advances, our understanding of the organization and functions of the BF cholinergic system mostly derives from nonhuman animal research. In this chapter, we begin with a review of the topographical organization of the BF cholinergic system in rodent and nonhuman primate models. We then discuss basic and clinical neuroscience research in humans, which has started to translate and extend the nonhuman animal research using novel noninvasive neuroimaging techniques. We focus on converging evidence indicating that the selective vulnerability of cholinergic neurons in Alzheimer's and Parkinson's diseases is expressed along a rostral-caudal topography in the BF. We close with a discussion of why this topography of vulnerability in the BF may occur and why it is relevant to the clinician.
基底前脑（BF）胆碱能系统由一群异质性的大型投射神经元组成，这些神经元支配着整个皮质层和杏仁核。胆碱能神经调节在调节认知和行为以及维持细胞内环境稳定方面起着关键作用。数十年来的尸检组织学研究表明，在诸如阿尔茨海默病和帕金森病等退行性疾病中，BF胆碱能神经元对衰老和与年龄相关的神经病理学具有选择性易损性。来自体内神经影像学研究的新证据允许对高危个体进行纵向追踪，表明胆碱能神经变性在这些疾病中可能比之前认为的发挥更早且更关键的作用。尽管有这些进展，但我们对BF胆碱能系统的组织和功能大多源于非人类动物研究。在本章中，我们首先回顾啮齿动物和非人类灵长类动物模型中BF胆碱能系统的拓扑组织。然后我们讨论人类的基础和临床神经科学研究，这些研究已开始使用新型非侵入性神经影像学技术来转化和扩展非人类动物研究。我们重点关注趋同证据表明阿尔茨海默病和帕金森病中胆碱能神经元的选择性易损性沿BF的头尾拓扑结构表现出来。最后我们讨论为什么BF中这种易损性拓扑结构会出现以及为什么它对临床医生很重要。
