2019年11月11日，美国范德比尔特大学医学中心Sachin Patel研究组在《自然—神经科学》在线发表论文，报道了不同恐惧状态下杏仁核基底外侧到中央谷氨酸能回路的动态重塑。

研究人员发现，条件性僵住行为的获得与基底外侧杏仁核（BLA）的相对兴奋性驱动的动态重塑有关，而恐惧清除训练则使该回路重塑为偏爱促肾上腺皮质激素释放因子表达阳性（CRF⁺）的神经元。重要的是，这种依赖经验的重塑需要BLA活性，而BLA与中央外侧杏仁核回路的直接抑制会损害恐惧记忆的获取和消退记忆的恢复。此外，CRF⁺神经元的异位兴奋削弱了恐惧记忆的获取并加速消失，而CRF⁺神经元抑制则削弱了消失记忆的恢复，这支持了CRF⁺神经元抑制习得性僵住行为的观点。这些数据表明，传入特定的动态重塑代表了经验依赖性行为选择修正背后的重要机制。

据了解，习得性恐惧反应的获取和消退利用了保守但灵活的神经回路。

附：英文原文

Title: Dynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states

Author: Nolan D. Hartley, Andrew D. Gaulden, Rita Bldi, Nathan D. Winters, Gregory J. Salimando, Luis Eduardo Rosas-Vidal, Alexis Jameson, Danny G. Winder, Sachin Patel

Issue&Volume: 2019-11-11

Abstract: Acquisition and extinction of learned fear responses utilize conserved but flexible neural circuits. Here we show that acquisition of conditioned freezing behavior is associated with dynamic remodeling of relative excitatory drive from the basolateral amygdala (BLA) away from corticotropin releasing factor-expressing (CRF+) centrolateral amygdala neurons, and toward non-CRF+ (CRF) and somatostatin-expressing (SOM+) neurons, while fear extinction training remodels this circuit back toward favoring CRF+ neurons. Importantly, BLA activity is required for this experience-dependent remodeling, while directed inhibition of the BLA–centrolateral amygdala circuit impairs both fear memory acquisition and extinction memory retrieval. Additionally, ectopic excitation of CRF+ neurons impairs fear memory acquisition and facilities extinction, whereas CRF+ neuron inhibition impairs extinction memory retrieval, supporting the notion that CRF+ neurons serve to inhibit learned freezing behavior. These data suggest that afferent-specific dynamic remodeling of relative excitatory drive to functionally distinct subcortical neuronal output populations represents an important mechanism underlying experience-dependent modification of behavioral selection.

DOI: 10.1038/s41593-019-0528-7

Source: https://www.nature.com/articles/s41593-019-0528-7