Reward Inhibits Paraventricular CRH Neurons to Relieve Stress

斯科普斯 神经科学 焦虑 生物 内科学 内分泌学 心理学 扁桃形结构 临床心理学 精神科 梅德林 医学 生物化学
作者
Yuan Yuan,Wéi Wú,Ming Chen,Fang Cai,Chengyu Fan,Wei L. Shen,Wenzhi Sun,Ji Hu
出处
期刊:Current Biology [Elsevier BV]
卷期号:29 (7): 1243-1251.e4 被引量:119
标识
DOI:10.1016/j.cub.2019.02.048
摘要

Chronic, uncontrollable stress can lead to various pathologies [1Foster J.A. Rinaman L. Cryan J.F. Stress & the gut-brain axis: regulation by the microbiome.Neurobiol. Stress. 2017; 7: 124-136Crossref PubMed Scopus (495) Google Scholar, 2Marcinkiewcz C.A. Mazzone C.M. D'Agostino G. Halladay L.R. Hardaway J.A. DiBerto J.F. Navarro M. Burnham N. Cristiano C. Dorrier C.E. et al.Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala.Nature. 2016; 537: 97-101Crossref PubMed Scopus (248) Google Scholar, 3Menard C. Pfau M.L. Hodes G.E. Kana V. Wang V.X. Bouchard S. Takahashi A. Flanigan M.E. Aleyasin H. LeClair K.B. et al.Social stress induces neurovascular pathology promoting depression.Nat. Neurosci. 2017; 20: 1752-1760Crossref PubMed Scopus (434) Google Scholar, 4Moloney R.D. O'Mahony S.M. Dinan T.G. Cryan J.F. Stress-induced visceral pain: toward animal models of irritable-bowel syndrome and associated comorbidities.Front. 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Corticotrophin-releasing hormone (CRH) neurons in paraventricular nucleus (PVN) represent a key neural population organizing endocrine, autonomic, and behavioral responses to stress by initiating hormonal cascades along the hypothalamic-pituitary-adrenal (HPA) axis and orchestrating stress-related behaviors through direct projections to limbic and autonomic brain centers [11Carlin K.M. Vale W.W. Bale T.L. Vital functions of corticotropin-releasing factor (CRF) pathways in maintenance and regulation of energy homeostasis.Proc. Natl. Acad. Sci. USA. 2006; 103: 3462-3467Crossref PubMed Scopus (47) Google Scholar, 12Füzesi T. Daviu N. Wamsteeker Cusulin J.I. Bonin R.P. Bains J.S. Hypothalamic CRH neurons orchestrate complex behaviours after stress.Nat. Commun. 2016; 7: 11937Crossref PubMed Scopus (137) Google Scholar, 13Kruk M.R. Westphal K.G. Van Erp A.M. van Asperen J. Cave B.J. Slater E. de Koning J. Haller J. 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Palatable foods, stress, and energy stores sculpt corticotropin-releasing factor, adrenocorticotropin, and corticosterone concentrations after restraint.Endocrinology. 2009; 150: 2325-2333Crossref PubMed Scopus (145) Google Scholar], it has remained unclear how these neurons respond dynamically to rewarding stimuli to mediate the stress-buffering effects of reward. Using fiber photometry of Ca2+ signals within genetically identified PVN CRH neurons in freely behaving mice [24Campos C.A. Bowen A.J. Roman C.W. Palmiter R.D. Encoding of danger by parabrachial CGRP neurons.Nature. 2018; 555: 617-622Crossref PubMed Scopus (131) Google Scholar, 25Gunaydin L.A. Grosenick L. Finkelstein J.C. Kauvar I.V. Fenno L.E. Adhikari A. Lammel S. Mirzabekov J.J. Airan R.D. Zalocusky K.A. et al.Natural neural projection dynamics underlying social behavior.Cell. 2014; 157: 1535-1551Abstract Full Text Full Text PDF PubMed Scopus (753) Google Scholar, 26Burkett J.P. Andari E. Johnson Z.V. Curry D.C. de Waal F.B. Young L.J. Oxytocin-dependent consolation behavior in rodents.Science. 2016; 351: 375-378Crossref PubMed Scopus (332) Google Scholar], we find that PVN CRH neurons are rapidly and strongly inhibited by reward consumption. Reward decreases anxiety-like behavior and stress-hormone surge induced by direct acute activation of PVN CRH neurons or repeated stress challenge. Repeated stress upregulates glutamatergic transmission and induces an N-methyl-D-aspartate receptor (NMDAR)-dependent burst-firing pattern in these neurons, whereas reward consumption rebalances the synaptic homeostasis and abolishes the burst firing. Anatomically, PVN CRH neurons integrate widespread information from both stress- and reward-related brain areas in the forebrain and midbrain, including multiple direct long-range GABAergic afferents. Together, these findings reveal a hypothalamic circuit that organizes adaptive stress response by complementarily integrating reward and stress signals and suggest that intervention in this circuit could provide novel methods to treat stress-related disorders.

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