TY - JOUR
T1 - Locus coeruleus anchors a trisynaptic circuit controlling fear-induced suppression of feeding
AU - Yang, Ben
AU - Sanches-Padilla, Javier
AU - Kondapalli, Jyothisri
AU - Morison, Sage L.
AU - Delpire, Eric
AU - Awatramani, Rajeshwar
AU - Surmeier, D. James
N1 - Funding Information:
We thank Kang Chen, Dannielle R. Schowalter, Marisha Alicea, and Bonnie M. Erjavec for genotyping and mouse colony management and Sasha Ulrich for lab management and administrative assistance. We thank Drs. Weixing Shen, Tamara Perez-Rosello, and Asami Tanimura for discussion and comments on the manuscript; Dr. Tristano Pancani for providing the drawing of a mouse in Illustrator; and all members of the Surmeier laboratory for their support. We especially thank Yu Chen for help with RT-PCR and Dannielle R. Schowalter for help with FC behavior experiments. We thank Dr. Jelena Radulovic for help with designing behavior tests and comments on the manuscript and her lab members, particularly Lynn Ren, for comments on the manuscript, and Dr. Craig Weiss, Mary Kando, and the Northwestern University Behavioral Phenotyping Core for help with FC behavior and data analysis. This work is supported in part by NIH Pre-Doctoral Training Grant NUIN-MRS T32 (to B.Y.) and by the DOD and the JPB Foundation (to D.J.S.). The CB1R lox/lox mouse generation was supported by the Gene-Targeted Mouse Core of the INIAstress Consortium, supported by National Institute on Alcohol Abuse and Alcoholism grant U01 AA013514 (to E.D.).
Funding Information:
We thank Kang Chen, Dannielle R. Schowalter, Marisha Alicea, and Bonnie M. Erjavec for genotyping and mouse colony management and Sasha Ulrich for lab management and administrative assistance. We thank Drs. Weixing Shen, Tamara Perez-Rosello, and Asami Tanimura for discussion and comments on the manuscript; Dr. Tristano Pancani for providing the drawing of a mouse in Illustrator; and all members of the Surmeier laboratory for their support. We especially thank Yu Chen for help with RT-PCR and Dannielle R. Schowalter for help with FC behavior experiments. We thank Dr. Jelena Radulovic for help with designing behavior tests and comments on the manuscript and her lab members, particularly Lynn Ren, for comments on the manuscript, and Dr. Craig Weiss, Mary Kando, and the Northwestern University Behavioral Phenotyping Core for help with FC behavior and data analysis. This work is supported in part by NIH Pre-Doctoral Training Grant NUIN-MRS T32 (to B.Y.) and by the DOD and the JPB Foundation (to D.J.S.). The CB1Rlox/lox mouse generation was supported by the Gene-Targeted Mouse Core of the INIAstress Consortium, supported by National Institute on Alcohol Abuse and Alcoholism grant U01 AA013514 (to E.D.). B.Y. designed the project, performed most experiments, and wrote the manuscript. J.S.-P. helped with some electrophysiological recordings. J.K. performed RT-PCR. S.L.M. performed TH immunostaining in TH-Flp;vGlut2-Cre;Ai65 mice. E.D. provided the CB1Rlox/lox animals. R.A. provided the TH-Flp;vGlut2-Cre and TH-Flp;vGlut2-Cre;Ai65 mice and discussed data. D.J.S. acquired funding, designed the project, and edited the manuscript. The authors declare no competing interests.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/3/3
Y1 - 2021/3/3
N2 - The circuit mechanisms underlying fear-induced suppression of feeding are poorly understood. To help fill this gap, mice were fear conditioned, and the resulting changes in synaptic connectivity among the locus coeruleus (LC), the parabrachial nucleus (PBN), and the central nucleus of amygdala (CeA)—all of which are implicated in fear and feeding—were studied. LC neurons co-released noradrenaline and glutamate to excite PBN neurons and suppress feeding. LC neurons also suppressed inhibitory input to PBN neurons by inducing heterosynaptic, endocannabinoid-dependent, long-term depression of CeA synapses. Blocking or knocking down endocannabinoid receptors in CeA neurons prevented fear-induced depression of CeA synaptic transmission and fear-induced suppression of feeding. Altogether, these studies demonstrate that LC neurons play a pivotal role in modulating the circuitry that underlies fear-induced suppression of feeding, pointing to new ways of alleviating stress-induced eating disorders.
AB - The circuit mechanisms underlying fear-induced suppression of feeding are poorly understood. To help fill this gap, mice were fear conditioned, and the resulting changes in synaptic connectivity among the locus coeruleus (LC), the parabrachial nucleus (PBN), and the central nucleus of amygdala (CeA)—all of which are implicated in fear and feeding—were studied. LC neurons co-released noradrenaline and glutamate to excite PBN neurons and suppress feeding. LC neurons also suppressed inhibitory input to PBN neurons by inducing heterosynaptic, endocannabinoid-dependent, long-term depression of CeA synapses. Blocking or knocking down endocannabinoid receptors in CeA neurons prevented fear-induced depression of CeA synaptic transmission and fear-induced suppression of feeding. Altogether, these studies demonstrate that LC neurons play a pivotal role in modulating the circuitry that underlies fear-induced suppression of feeding, pointing to new ways of alleviating stress-induced eating disorders.
KW - amygdala
KW - cannabinoid receptors
KW - fear
KW - feeding
KW - locus coeruleus
KW - long-term depression
KW - neurotransmitter co-release
KW - parabrachial nucleus
KW - synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=85100687333&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100687333&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2020.12.023
DO - 10.1016/j.neuron.2020.12.023
M3 - Article
C2 - 33476548
AN - SCOPUS:85100687333
SN - 0896-6273
VL - 109
SP - 823-838.e6
JO - Neuron
JF - Neuron
IS - 5
ER -