Early life adversity decreases pre-adolescent fear expression by accelerating amygdala PV cell development
Early life adversity decreases pre-adolescent fear expression by accelerating amygdala PV cell development
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DOI：
10.7554/elife.55263
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发表时间：
2020-07-21
期刊：
影响因子：
7.7
通讯作者：
Bath, Kevin G.
中科院分区：
文献类型：
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作者：
Nieves, Gabriela Manzano;Bravo, Marilyn;Bath, Kevin G.
早期生活逆境（ELA）与以后生活中压力相关疾病的风险增加有关。ELA与精神病理风险之间的联系已得到证实，但其发展机制尚不清楚。采用资源不安全、有限床上用品（LB）小鼠模型，研究了LB对恐惧学习和情绪调节相关神经元结构、内侧前额叶皮层（mPFC）和杏仁核基底外侧（BLA）发育的影响。LB延缓了断奶期（21日龄）小鼠表达听觉条件恐惧记忆的能力，但不能形成听觉条件恐惧记忆。LB加速了BLA中小白蛋白（PV）阳性细胞的发育出现，并增加了PL和BLA之间的解剖联系。通过光基因灭活BLA中pv阳性细胞，恢复LB小鼠的恐惧表达。目前的研究结果提供了一种模型，即在发育早期短暂的情绪反应迟钝，在青春期后期出现潜在的与恐惧相关的记忆。
Early life adversity (ELA) is associated with increased risk for stress-related disorders later in life. The link between ELA and risk for psychopathology is well established but the developmental mechanisms remain unclear. Using a mouse model of resource insecurity, limited bedding (LB), we tested the effects of LB on the development of fear learning and neuronal structures involved in emotional regulation, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). LB delayed the ability of peri-weanling (21 days old) mice to express, but not form, an auditory conditioned fear memory. LB accelerated the developmental emergence of parvalbumin (PV)-positive cells in the BLA and increased anatomical connections between PL and BLA. Fear expression in LB mice was rescued through optogenetic inactivation of PV-positive cells in the BLA. The current results provide a model of transiently blunted emotional reactivity in early development, with latent fear-associated memories emerging later in adolescence.