CRF signaling between neurons in the paraventricular nucleus of the hypothalamus (PVN) coordinates stress responses
CRF signaling between neurons in the paraventricular nucleus of the hypothalamus (PVN) coordinates stress responses
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DOI：
10.1016/j.ynstr.2019.100192
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发表时间：
2019-11-01
影响因子：
5
通讯作者：
Justice, Nicholas J.
中科院分区：
文献类型：
--
作者：
Jiang, Zhiying;Rajamanickam, Shivakumar;Justice, Nicholas J.
精确协调神经内分泌、自主神经和行为应激反应的重要性是2018年应激神经生物学研讨会的主要主题，该研讨会在加拿大阿尔伯塔班夫省立公园美丽的环境中举行。这次会议的大部分研究强调了适当应对压力的重要性，以避免各种神经精神疾病，包括创伤后应激障碍（PTSD），抑郁症和成瘾。下丘脑室旁核（paraventricular nucleus of the hypothalamus，PVN）中的促肾上腺皮质激素释放因子（Corticotropin-Releasing Factor，CRF）神经元是应激反应的中枢参与者，整合外部和内脏应激相关信息，然后通过PVN的内分泌和神经输出指导神经内分泌、自主神经和行为适应。PVN包含密集排列的对应激做出反应的神经元类型，包括激活下丘脑-垂体-肾上腺（HPA）轴的CRF神经元。最近，在PVN中鉴定出表达CRF受体1（CRFR 1）的新的神经元群体表明，PVN中的CRF释放向邻近的CRF响应神经元发出信号，潜在地在HPA轴反馈、神经内分泌协调和自主信号传导中起作用。在这里，我们回顾了我们最近的工作，其特征在于PVN内微电路，其中局部释放的CRF释放激活CRFR 1+神经元，使CRF神经元上的反复抑制性GABA能突触抑制兴奋性，从而限制HPA轴过度活跃，以响应压力，促进压力恢复，我们在会议的海报会议上提出。然后，我们讨论的问题，已经出现了出版后，我们的初步表征的微电路，关于特定功能的PVN内CRF信号和其潜在的作用，协调神经内分泌，自主神经和行为输出的PVN。我们提出的工作，以及2018年应激神经生物学研讨会上的许多演讲，共同建立了PVN内信号传导作为应激反应途径中的重要调控节点，这是神经精神疾病发病机制的核心。
The importance of a precisely coordinated neuroendocrine, autonomic, and behavioral stress response was a primary theme at the Stress Neurobiology Workshop 2018, held in the beautiful setting of Banff Provincial Park in Alberta, Canada. Much of the research featured at this meeting reinforced the importance of appropriately responding to stress in order to avoid various neuropsychiatric pathologies, including Post-Traumatic Stress Disorder (PTSD), depression, and addiction. Corticotropin-Releasing Factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVN) are central players in the stress response, integrating both external and visceral stress-relevant information, then directing neuroendocrine, autonomic and behavioral adaptations via endocrine and neural outputs of the PVN. The PVN contains a densely packed array of neuron types that respond to stress, including CRF neurons that activate the Hypothalamic-Pituitary-Adrenal (HPA) axis. Recently, identification of a new population of neurons in the PVN that express CRF Receptor 1 (CRFR1) has suggested that CRF release in the PVN signals to neighboring CRF responsive neurons, potentially functioning in HPA axis feedback, neuroendocrine coordination, and autonomic signaling. Here, we review our recent work characterizing an intra-PVN microcircuit in which locally released CRF release activates CRFR1 + neurons that make recurrent inhibitory GABAergic synapses onto CRF neurons to dampen excitability, therebylimiting HPA axis hyperactivity in response to stress and promoting stress recovery, which we presented in a poster session at the conference. We then discuss questions that have arisen following publication of our initial characterization of the microcircuit, regarding specific features of intra-PVN CRF signaling and its potential role in coordinating neuroendocrine, autonomic, and behavioral outputs of the PVN. Our presented work, as well as many of the presentations at the Stress Neurobiology Workshop 2018 together establish intra-PVN signaling as an important regulatory node in stress response pathways, which are central to the pathogenesis of neuropsychiatric disorders.