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.

精确协调的神经内分泌，自主神经和行为应激反应的重要性是在加拿大艾伯塔省班夫省立公园美丽环境中举办的2018应激神经生物学研讨会的主题。本次会议上进行的许多研究都强调了对压力做出适当反应的重要性，以避免各种神经精神疾病，包括创伤后应激障碍（PTSD），抑郁和成瘾。下丘脑室旁核（PVN）中的促肾上腺皮质激素释放因子（CRF）神经元是应激反应的主要参与者，整合了与内脏和内脏应激相关的信息，然后通过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。PVN包含一系列密集的神经元类型，这些神经元类型可对压力作出反应，包括激活下丘脑-垂体-肾上腺（HPA）轴的CRF神经元。最近，鉴定出表达CRF受体1（CRFR1）的PVN中新的神经元群体表明，CRF在PVN信号中释放给邻近的CRF反应性神经元，可能在HPA轴反馈，神经内分泌协调和自主信号中起作用。在这里，我们回顾了我们最近的研究工作，研究了PVN内微电路的特征，其中局部释放的CRF释放激活CRFR1 +神经元，从而使抑制性GABA能突触反复出现在CRF神经元上，从而抑制兴奋性，从而限制HPA轴对应激的过度反应并促进应激恢复，在会议的海报会议上介绍。然后，我们讨论在公布微电路的初始特性之后出现的问题，这些问题涉及PVN内CRF信号传导的具体特征及其在协调神经内分泌，自主神经和行为输出方面的潜在作用。我们的研究成果以及2018年应激神经生物学研讨会上的许多演讲共同将PVN内信号传导确立为应激反应途径中的重要调节节点，这是神经精神疾病的发病机制的关键。