中文摘要
恐惧是动物体为了减少伤害和保证存活而对外界刺激产生防御性行为的一种生死攸关的情绪反应。而前额叶皮层(mPFC)-腹外侧杏仁核(BLA)环路是调控恐惧条件化的主要神经环路。乙酰胆碱是调控行为的基本神经递质之一, 皮层胆碱投射主要来源于基底前脑(BF)胆碱能神经元,其丢失被认为与认知障碍有关。调控BF胆碱能神经元不仅可调节皮层的突触可塑性来调控学习, 而且可直接调控BLA神经环路突触可塑性控制恐惧学习。但BF胆碱能的皮层投射调控恐惧行为及其神经环路机制仍不明晰。本研究结合在体光遗传学技术与多道电生理技术,清醒活体状态光遗传调控BF胆碱能胞体或者mPFC投射末梢来控制恐惧行为变化,同时记录mPFC神经元活性变化以及场电位,对比分析mPFC的神经微环路神经元在BF胆碱能局部或整体光刺激下调控恐惧行为中的动态变化及集群信息编码。期待阐明胆碱系统对mPFC恐惧神经微环路的动态调控编码机制。
英文摘要
Fear emotionally elicits defensive behavioral responses that have evolved to enable the animals to avoid or reduce harm and thus ensure its survival. Fear behavior is known to depend on the interaction between the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) neuronal circuits. Cholinergic signaling has long been implicated in attending and remembering emotionally potent experiences. Basal forebrain (BF) is best known brain areas for acetylcholine containing neurons that provide most of the cholinergic innervation of the neocortex. The degeneration of the cholinergic neurons in BF is correlated with Alzheimer’s disease and forms of dementia and is associated with normal cognitive aging. BF cholinergic neurons encode a precisely timed signal and modulate the neocortex signals and thereby could support learning and plasticity as a reinforcement signal. Also cholinergic modulate of BLA circuits in the inscription and retention of fear memories. but the precise role of ACh signaling in neocortex especially in mPFC circuits in fear processing and behavior has remained elusive. We combined with in vivo behaving optogenetics and multi-channel electrophysiological techniques, selective specific regulation of BF cholinergic neuron activity in BF or in mPFC of the terminals of the neurons, while using electrophysiological techniques to record mPFC neurons activities and field potential changes in fear condition. After that, analysis and compare the dynamic changes and information coding of the mPFC neuronal microcircuits correlate to fear condition during the local modulation of terminals of the cholinergic neurons and the entire circuit modulation of the BF cholinergic neurons. Looking for revealing the dynamical neuronal mechanisms of BF cholinergic system regulate the fear learning & memory in the mPFC neuronal circuits.
