Dopamine-dependent synaptic plasticity in an amygdala inhibitory circuit controls fear memory expression
Dopamine-dependent synaptic plasticity in an amygdala inhibitory circuit controls fear memory expression
复制标题
DOI：
10.5483/bmbrep.2016.49.1.258
复制
发表时间：
2016-01-01
期刊：
影响因子：
3.8
通讯作者：
Kim, Joung-Hun
中科院分区：
文献类型：
--
作者：
Lee, Joo Han;Kim, Joung-Hun
在日常生活中发生的许多事件中，我们很容易记住重要的信息，但不能长时间记住大多数不太重要的事件。尽管一些情节包含假定的情感方面，但较低显著性的信息很少通过未知机制存储在神经回路中。我们提供的大量证据表明，杏仁核背侧ITC的突触可塑性允许选择性地存储突出的情绪体验，同时阻止不太突出的体验进入长期记忆。在激活D4R或弱恐惧条件反射后，STDP刺激诱发LA-ITC突触的LTD。这种形式的LTD依赖于突触前D4R，可能是GABA释放增强的结果。光遗传学消除LTD和消除ITC背侧的D4R都会导致体内恐惧反应的增强和过度广泛。最后，我们证明了PTSD模型小鼠背侧ITC的LTD受损，这表明gaba能信号的不适应和由此产生的LTD损伤参与了PTSD的内表型。
Of the numerous events that occur in daily life, we readily remember salient information, but do not retain most less-salient events for a prolonged period. Although some of the episodes contain putatively emotional aspects, the information with lower saliency is rarely stored in neural circuits via an unknown mechanism. We provided substantial evidence indicating that synaptic plasticity in the dorsal ITC of amygdala allows for selective storage of salient emotional experiences, while it deters less-salient experience from entering long-term memory. After activation of D4R or weak fear conditioning, STDP stimulation induces LTD in the LA-ITC synapses. This form of LTD is dependent upon presynaptic D4R, and is likely to result from enhancement of GABA release. Both optogenetic abrogation of LTD and ablation of D4R at the dorsal ITC in vivo lead to heightened and over-generalized fear responses. Finally, we demonstrated that LTD was impaired at the dorsal ITC of PTSD model mice, which suggests that maladaptation of GABAergic signaling and the resultant LTD impairment contribute to the endophenotypes of PTSD.