Luchicchi Antonio, Bloem Bernard, Viaña John Noel M, Mansvelder Huibert D, Role Lorna W
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Netherlands.
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Netherlands ; McGovern Institute for Brain Research, Massachusetts Institute of Technology Cambridge, MA, USA.
Front Synaptic Neurosci. 2014 Oct 27;6:24. doi: 10.3389/fnsyn.2014.00024. eCollection 2014.
Acetylcholine (ACh) signaling underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. Alterations in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric disorders. In the central nervous system, ACh transmission is mainly guaranteed by dense innervation of select cortical and subcortical regions from disperse groups of cholinergic neurons within the basal forebrain (BF; e.g., diagonal band, medial septal, nucleus basalis) and the pontine-mesencephalic nuclei, respectively. Despite the fundamental role of cholinergic signaling in the CNS and the long standing knowledge of the organization of cholinergic circuitry, remarkably little is known about precisely how ACh release modulates cortical and subcortical neural activity and the behaviors these circuits subserve. Growing interest in cholinergic signaling in the CNS focuses on the mechanism(s) of action by which endogenously released ACh regulates cognitive functions, acting as a neuromodulator and/or as a direct transmitter via nicotinic and muscarinic receptors. The development of optogenetic techniques has provided a valuable toolbox with which we can address these questions, as it allows the selective manipulation of the excitability of cholinergic inputs to the diverse array of cholinergic target fields within cortical and subcortical domains. Here, we review recent papers that use the light-sensitive opsins in the cholinergic system to elucidate the role of ACh in circuits related to attention and emotionally salient behaviors. In particular, we highlight recent optogenetic studies which have tried to disentangle the precise role of ACh in the modulation of cortical-, hippocampal- and striatal-dependent functions.
乙酰胆碱（ACh）信号传导是认知功能和行为特定方面的基础，包括注意力、学习、记忆和动机。ACh信号传导的改变涉及多种神经精神疾病的病理生理学。在中枢神经系统中，ACh传递主要分别由基底前脑（BF；例如斜角带、内侧隔核、基底核）内分散的胆碱能神经元群以及脑桥 - 中脑核团对特定皮质和皮质下区域的密集支配来保证。尽管胆碱能信号在中枢神经系统中具有重要作用，并且人们对胆碱能神经回路的组织已有长期了解，但对于ACh释放究竟如何调节皮质和皮质下神经活动以及这些回路所支持的行为，却知之甚少。对中枢神经系统中胆碱能信号传导的兴趣日益增加，重点在于内源性释放的ACh作为神经调节剂和/或通过烟碱受体和毒蕈碱受体作为直接递质来调节认知功能的作用机制。光遗传学技术的发展提供了一个有价值的工具包，借助它我们可以解决这些问题，因为它允许选择性地操纵胆碱能输入到皮质和皮质下区域内各种胆碱能靶场的兴奋性。在这里，我们回顾了最近使用胆碱能系统中光敏感视蛋白来阐明ACh在与注意力和情绪突出行为相关回路中的作用的论文。特别是，我们重点介绍了最近的光遗传学研究，这些研究试图厘清ACh在调节皮质、海马和纹状体依赖性功能方面的确切作用。
