PMID- 30853436
OWN - NLM
STAT- MEDLINE
DCOM- 20200413
LR  - 20200413
IS  - 1879-0445 (Electronic)
IS  - 0960-9822 (Linking)
VI  - 29
IP  - 7
DP  - 2019 Apr 1
TI  - Reward Inhibits Paraventricular CRH Neurons to Relieve Stress.
PG  - 1243-1251.e4
LID - S0960-9822(19)30218-0 [pii]
LID - 10.1016/j.cub.2019.02.048 [doi]
AB  - Chronic, uncontrollable stress can lead to various pathologies [1-6]. Adaptive 
      behaviors, such as reward consumption, control excessive stress responses and 
      promote positive health outcomes [3, 7-10]. 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 [11-18]. Although stress and reward have been reported to 
      induce changes of c-Fos and CRH expression in PVN CRH neurons [19-23], it has 
      remained unclear how these neurons respond dynamically to rewarding stimuli to 
      mediate the stress-buffering effects of reward. Using fiber photometry of Ca(2+) 
      signals within genetically identified PVN CRH neurons in freely behaving mice 
      [24-26], 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.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Yuan, Yuan
AU  - Yuan Y
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, 
      China; Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, 
      China; University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Wu, Wei
AU  - Wu W
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, 
      China; iHuman Institute, ShanghaiTech University, Shanghai 201210, China; 
      Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China; 
      University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Chen, Ming
AU  - Chen M
AD  - iHuman Institute, ShanghaiTech University, Shanghai 201210, China.
FAU - Cai, Fang
AU  - Cai F
AD  - iHuman Institute, ShanghaiTech University, Shanghai 201210, China.
FAU - Fan, Chengyu
AU  - Fan C
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, 
      China.
FAU - Shen, Wei
AU  - Shen W
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, 
      China.
FAU - Sun, Wenzhi
AU  - Sun W
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, 
      China; iHuman Institute, ShanghaiTech University, Shanghai 201210, China; Chinese 
      Institute for Brain Research, Beijing 102206, China. Electronic address: 
      sunwenzhi@cibr.ac.cn.
FAU - Hu, Ji
AU  - Hu J
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, 
      China. Electronic address: huji@shanghaitech.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190307
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
CIN - Nat Rev Neurosci. 2019 May;20(5):250-251. PMID: 30886363
MH  - Animals
MH  - Corticotropin-Releasing Hormone/*metabolism
MH  - Male
MH  - Mice
MH  - Neurons/*physiology
MH  - Paraventricular Hypothalamic Nucleus/*physiology
MH  - *Reward
MH  - Stress, Psychological/*metabolism
OTO - NOTNLM
OT  - burst firing
OT  - calcium signal
OT  - corticotrophin-releasing hormone
OT  - fiber photometry
OT  - monosynaptic retrograde tracing
OT  - neural circuits
OT  - paraventricular nucleus of hypothalamus
OT  - reward
OT  - stress
OT  - synaptic transmission
EDAT- 2019/03/12 06:00
MHDA- 2020/04/14 06:00
CRDT- 2019/03/12 06:00
PHST- 2019/02/02 00:00 [received]
PHST- 2019/02/15 00:00 [revised]
PHST- 2019/02/20 00:00 [accepted]
PHST- 2019/03/12 06:00 [pubmed]
PHST- 2020/04/14 06:00 [medline]
PHST- 2019/03/12 06:00 [entrez]
AID - S0960-9822(19)30218-0 [pii]
AID - 10.1016/j.cub.2019.02.048 [doi]
PST - ppublish
SO  - Curr Biol. 2019 Apr 1;29(7):1243-1251.e4. doi: 10.1016/j.cub.2019.02.048. Epub 
      2019 Mar 7.