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Regulation of Hypothalamo-Pituitary-Adrenocortical Responses to Stressors by the Nucleus of the Solitary Tract/Dorsal Vagal Complex

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Abstract

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.

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Acknowledgements

I am grateful for the inspiration provided by my friend and colleague Richard Kvetnansky, both for the studies contributing to this review and for my career in general. He was a major force in the stress field, and his leadership and support will be sorely missed. In addition, I would like to acknowledge all of the trainees and staff that have contributed to these studies, initiated at the University of Kentucky and continued on at the University of Cincinnati. Work on these studies was supported by MH049698 and MH069860.

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  1. 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

    James P. Herman

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Herman, J.P. Regulation of Hypothalamo-Pituitary-Adrenocortical Responses to Stressors by the Nucleus of the Solitary Tract/Dorsal Vagal Complex. Cell Mol Neurobiol 38, 25–35 (2018). https://doi.org/10.1007/s10571-017-0543-8

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