Cholinergic regulation of fear learning and extinction.
Cholinergic regulation of fear learning and extinction.
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DOI：
10.1002/jnr.23840
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发表时间：
2017-03
影响因子：
4.2
通讯作者：
Fadel JR
中科院分区：
文献类型：
--
作者：
Wilson MA;Fadel JR
胆碱能激活调节认知功能，尤其是长期记忆的巩固。在这里，我们概述了支持胆碱能调节巴甫洛夫情境和线索条件恐惧学习和消退的解剖学、神经化学和药理学证据。基底前脑胆碱能神经元向新皮质区和皮层下边缘结构（如海马和杏仁核）提供输入。毒蕈碱和烟碱受体的药理学操作支持杏仁核、海马体和前额皮质胆碱能过程在调节与威胁相关的背景或线索的学习和消除中的作用。来自病变研究和使用微透析对体内乙酰胆碱释放的分析的其他证据同样支持胆碱能神经传递在获得恐惧消退过程中在皮质-杏仁核或皮质-海马回路中的关键作用。尽管一些研究表明胆碱能神经传递在细胞可塑性中扮演着复杂的角色，但需要更多的工作来阐明胆碱能的确切机制以及毒蕈碱和烟碱受体在这些恐惧回路中的生理作用。这些研究对于阐明胆碱能神经传递在创伤后应激障碍（PTSD）等涉及灭绝学习缺陷的疾病中的作用以及为此类疾病开发新的治疗方法具有重要意义。
Cholinergic activation regulates cognitive function, and particularly long term memory consolidation. Here we present an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat. Additional evidence from lesion studies and analysis of in vivo acetylcholine release using microdialysis similarly support a critical role of cholinergic neurotransmission in cortico-amygdalar or cortico-hippocampal circuits during acquisition of fear extinction. Although a few studies suggest a complex role of cholinergic neurotransmission in the cellular plasticity needed for extinction learning, more work is needed to elucidate the exact cholinergic mechanisms and physiological role of muscarinic and nicotinic receptors in these fear circuits. Such studies will be important for elucidating the role of cholinergic neurotransmission in disorders such as post-traumatic stress disorder (PTSD) that involve deficits in extinction learning as well as developing novel therapeutic approaches for such disorders.