Programming of Stress-Sensitive Neurons and Circuits by Early-Life Experiences
Programming of Stress-Sensitive Neurons and Circuits by Early-Life Experiences
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DOI：
10.3389/fnbeh.2019.00030
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发表时间：
2019-02-18
影响因子：
3
通讯作者：
Baram, Tallie Z.
中科院分区：
文献类型：
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作者：
Bolton, Jessica L.;Short, Annabel Katherine;Baram, Tallie Z.
早期生活经历长期影响大脑结构和功能，有助于对压力和压力相关障碍的恢复或脆弱。因此，了解早期生活经历对特定脑细胞和脑回路进行编程以塑造终身认知和情感功能的机制至关重要。我们发现下丘脑室旁核(PVN)中的促肾上腺皮质激素释放激素(CRH)表达神经元的数量是早期生活经验的一个关键的早期目标。不利的经历增加了对PVN CRH细胞的兴奋性神经传递，而最佳的经历，如加强和可预测的产妇护理，减少了谷氨酸能输入到该细胞群体的数量和功能。突触神经传递的改变足以在CRH表达的神经元内启动大规模、持久的表观遗传重新编程，与应激恢复和额外的认知和情绪结果相关。因此，早期生活经历影响大脑的机制为干预提供了容易处理的目标。
Early-life experiences influence brain structure and function long-term, contributing to resilience or vulnerability to stress and stress-related disorders. Therefore, understanding the mechanisms by which early-life experiences program specific brain cells and circuits to shape life-long cognitive and emotional functions is crucial. We identify the population of corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamic paraventricular nucleus (PVN) as a key, early target of early-life experiences. Adverse experiences increase excitatory neurotransmission onto PVN CRH cells, whereas optimal experiences, such as augmented and predictable maternal care, reduce the number and function of glutamatergic inputs onto this cell population. Altered synaptic neurotransmission is sufficient to initiate large-scale, enduring epigenetic re-programming within CRH-expressing neurons, associated with stress resilience and additional cognitive and emotional outcomes. Thus, the mechanisms by which early-life experiences influence the brain provide tractable targets for intervention.