Genetically and functionally defined NTS to PBN brain circuits mediating anorexia.
The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRP(PBN)) neurons; however, the molecular identity of the inputs to these neurons was not established. Here we identify cholecystokinin (CCK) and noradrenergic, dopamine β-hydroxylase (DBH)-expressing NTS neurons as two separate populations that directly excite CGRP(PBN) neurons. When these NTS neurons are activated using optogenetic or chemogenetic methods, food intake decreases and with chronic stimulation mice lose body weight. Our optogenetic results reveal that CCK and DBH neurons in the NTS directly engage CGRP(PBN) neurons to promote anorexia.
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Carolyn W
CW
Roman
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.|Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Victor A
VA
Derkach
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.|Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Richard D
RD
Palmiter
D000200:Action Potentials; D000818:Animals; D000855:Anorexia / Q000235:genetics* / Q000503:physiopathology*; D001007:Anxiety / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004435:Eating; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism; D065823:Parabrachial Nucleus / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017552:Solitary Nucleus / Q000503:physiopathology*
D016760:Proto-Oncogene Proteins c-fos; D002766:Cholecystokinin; D004299:Dopamine beta-Hydroxylase; D015740:Calcitonin Gene-Related Peptide