Dynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states.,Nature Neuroscience

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Dynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states.
Nature Neuroscience ( IF 21.2 ) Pub Date : 2019-11-11 , DOI: 10.1038/s41593-019-0528-7
Nolan D Hartley _{1,

2} , Andrew D Gaulden ₁ , Rita Báldi ₁ , Nathan D Winters _{1,

3} , Gregory J Salimando _{2,

4} , Luis Eduardo Rosas-Vidal ₁ , Alexis Jameson _{1,

2} , Danny G Winder _{1,

2,

3,

4} , Sachin Patel _{1,

2,

3,

4}

Affiliation

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.

中文翻译：

跨越恐惧状态的基底外侧到中央杏仁核谷氨酸回路的动态重塑。

习得的恐惧反应的获得和消除利用了保守但灵活的神经回路。在这里，我们发现条件性冻结行为的获得与基底外侧杏仁核（BLA）的相对兴奋驱动的动态重塑相关，该驱动远离表达促肾上腺皮质激素释放因子（CRF+）的中央外侧杏仁核神经元，并朝向非CRF+（CRF-）和生长抑素-表达 (SOM+) 神经元，而恐惧消退训练则将该回路重塑回有利于 CRF+ 神经元的方向。重要的是，BLA 活性是这种依赖于经验的重塑所必需的，而直接抑制 BLA 中央外侧杏仁核回路会损害恐惧记忆的获取和消退记忆的检索。此外，CRF+神经元的异位兴奋会损害恐惧记忆的获得并促进消退，而CRF+神经元的抑制会损害消退记忆的检索，这支持了CRF+神经元有助于抑制习得的冻结行为的观点。这些数据表明，对功能不同的皮层下神经元输出群体的相对兴奋驱动的传入特异性动态重塑代表了行为选择的经验依赖性修改的重要机制。

更新日期：2019-11-13

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