Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits.
Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits.
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DOI：
10.1016/j.neuron.2016.04.028
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发表时间：
2016-06-01
期刊：
影响因子：
16.2
通讯作者：
Role LW
中科院分区：
文献类型：
--
作者：
Jiang L;Kundu S;Lederman JD;López-Hernández GY;Ballinger EC;Wang S;Talmage DA;Role LW
我们通过对基底外侧杏仁核（BLA）胆碱能输入的光遗传学调节，研究了内源性胆碱能信号对恐惧相关记忆获得和消退的贡献。刺激BLA内的胆碱能终端领域在清醒的行为小鼠在训练过程中的线索恐惧条件反射范式减缓灭绝的学习恐惧的测定多日保留灭绝学习。在训练过程中抑制胆碱能活动减少了习得性恐惧行为的获得。在BLA的胆碱能信号的行为效应的电路机制进行了评估，在体内和离体电生理记录。内源性胆碱能输入的光刺激：（1）通过激活乙酰胆碱受体（AChR）增强假定的BLA主神经元的放电;（2）增强BLA中的突触传递;（3）诱导皮质-杏仁核回路的LTP。这些研究支持BLA回路的胆碱能调节在恐惧记忆的铭刻和保留中的重要作用。
We examined the contribution of endogenous cholinergic signaling to the acquisition and extinction of fear- related memory by optogenetic regulation of cholinergic input to the basal lateral amygdala (BLA). Stimulation of cholinergic terminal fields within the BLA in awake-behaving mice during training in a cued fear-conditioning paradigm slowed the extinction of learned fear as assayed by multi-day retention of extinction learning. Inhibition of cholinergic activity during training reduced the acquisition of learned fear behaviors. Circuit mechanisms underlying the behavioral effects of cholinergic signaling in the BLA were assessed by in vivo and ex vivo electrophysiological recording. Photo-stimulation of endogenous cholinergic input: (1) enhances firing of putative BLA principal neurons through activation of acetylcholine receptors (AChRs); (2) enhances glutamatergic synaptic transmission in the BLA and (3) induces LTP of cortical-amygdala circuits. These studies support an essential role of cholinergic modulation of BLA circuits in the inscription and retention of fear memories.