Stress Neurobiology Laboratory, Department of Psychiatry and Behavioral Neuroscience, UC Neurobiology Research Center, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH, 45237-0506, USA.
Cell Mol Neurobiol. 2018 Jan;38(1):25-35. doi: 10.1007/s10571-017-0543-8. Epub 2017 Sep 11.
Hindbrain neurons in the nucleus of the solitary tract (NTS) are critical for regulation of hypothalamo-pituitary-adrenocortical (HPA) responses to stress. It is well known that noradrenergic (as well as adrenergic) neurons in the NTS send direct projections to hypophysiotropic corticotropin-releasing hormone (CRH) neurons and control activation of HPA axis responses to acute systemic (but not psychogenic) stressors. Norepinephrine (NE) signaling via alpha1 receptors is primarily excitatory, working either directly on CRH neurons or through presynaptic activation of glutamate release. However, there is also evidence for NE inhibition of CRH neurons (possibly via beta receptors), an effect that may occur at higher levels of stimulation, suggesting that NE effects on the HPA axis may be context-dependent. Lesions of ascending NE inputs to the paraventricular nucleus attenuate stress-induced ACTH but not corticosterone release after chronic stress, indicating reduction in central HPA drive and increased adrenal sensitivity. Non-catecholaminergic NTS glucagon-like peptide 1/glutamate neurons play a broader role in stress regulation, being important in HPA activation to both systemic and psychogenic stressors as well as HPA axis sensitization under conditions of chronic stress. Overall, the data highlight the importance of the NTS as a key regulatory node for coordination of acute and chronic stress.
孤束核中的后脑神经元对于调节下丘脑-垂体-肾上腺皮质轴（HPA）对压力的反应至关重要。众所周知，孤束核中的去甲肾上腺素能（以及肾上腺素能）神经元向促肾上腺皮质激素释放激素（CRH）神经元直接投射，并控制 HPA 轴对急性全身（而非精神性）应激源的反应的激活。通过 alpha1 受体的去甲肾上腺素信号主要是兴奋性的，它可以直接作用于 CRH 神经元，也可以通过谷氨酸释放的突触前激活来作用。然而，也有证据表明去甲肾上腺素抑制 CRH 神经元（可能通过 beta 受体），这种效应可能发生在更高的刺激水平，表明去甲肾上腺素对 HPA 轴的影响可能是上下文相关的。向室旁核上升的去甲肾上腺素输入的损伤减弱了应激诱导的 ACTH 释放，但不能减弱慢性应激后的皮质酮释放，这表明中枢 HPA 驱动的减少和肾上腺敏感性的增加。非儿茶酚胺能孤束核胰高血糖素样肽 1/谷氨酸神经元在应激调节中发挥着更广泛的作用，对于全身和精神性应激源以及慢性应激条件下 HPA 轴的敏感化，它们对于 HPA 轴的激活都很重要。总的来说，这些数据强调了孤束核作为协调急性和慢性应激的关键调节节点的重要性。
