Genetic identification of a neural circuit that suppresses appetite

• Published in: Nature (London) 2013-11, Vol.503 (7474), p.111-114
• Main Authors: Carter, Matthew E., Soden, Marta E., Zweifel, Larry S., Palmiter, Richard D.
• Format: Article
• Language: English
• Subjects: 631/378/1488/393; Amygdala - anatomy & histology; Amygdala - cytology; Amygdala - drug effects; Amygdala - physiology; Animals; Appetite; Appetite - drug effects; Appetite - genetics; Appetite - physiology; Bacterial diseases; Biological and medical sciences; Calcitonin Gene-Related Peptide - metabolism; Eating - drug effects; Eating - genetics; Eating - physiology; Female; Food; Fundamental and applied biological sciences. Psychology; Gene expression; Genetic aspects; Hormones; Humanities and Social Sciences; Identification and classification; letter; Lithium; Male; Medical sciences; Mice; Mice, Inbred C57BL; multidisciplinary; Neural circuitry; Neural Pathways - drug effects; Neural Pathways - physiology; Neurogenetics; Neurons; Neurons - drug effects; Neuropharmacology; Optogenetics; Pharmacology. Drug treatments; Pons - anatomy & histology; Pons - cytology; Pons - drug effects; Pons - physiology; Proto-Oncogene Proteins c-fos - metabolism; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Psychophysiology; Rodents; Satiety Response - drug effects; Satiety Response - physiology; Science; Starvation; Starvation - drug therapy; Toxins; Vertebrates: nervous system and sense organs; Weight control
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12596

A neural circuit from the parabrachial nucleus to the central nucleus of the amygdala mediates appetite suppression. Neural circuitry closely linked to appetite modulation The parabrachial nucleus (PBN) is an area of the brainstem containing subpopulations of neurons associated with taste, sodium intake, respiration, pain, thermosensation and appetite suppression. Partly because of the heterogeneous mix of cells making up this structure, it has proved difficult to identify the specific pathways driving appetite suppression. Now, using a variety of tools including optogenetic and pharmacogenetic analysis, Richard Palmiter and colleagues identify active calcitonin gene-related peptide-expressing neurons, projecting from the PBN to the central nucleus of the amygdala as a critical circuit driving appetite suppression. By contrast, inhibition of these neurons leads to increased feeding, suggesting that this neural circuit may provide targets for therapeutic intervention to both suppress and promote appetite. Appetite suppression occurs after a meal and in conditions when it is unfavourable to eat, such as during illness or exposure to toxins. A brain region proposed to play a role in appetite suppression is the parabrachial nucleus 1 , 2 , 3 , a heterogeneous population of neurons surrounding the superior cerebellar peduncle in the brainstem. The parabrachial nucleus is thought to mediate the suppression of appetite induced by the anorectic hormones amylin and cholecystokinin 2 , as well as by lithium chloride and lipopolysaccharide, compounds that mimic the effects of toxic foods and bacterial infections, respectively 4 , 5 , 6 . Hyperactivity of the parabrachial nucleus is also thought to cause starvation after ablation of orexigenic agouti-related peptide neurons in adult mice 1 , 7 . However, the identities of neurons in the parabrachial nucleus that regulate feeding are unknown, as are the functionally relevant downstream projections. Here we identify calcitonin gene-related peptide-expressing neurons in the outer external lateral subdivision of the parabrachial nucleus that project to the laterocapsular division of the central nucleus of the amygdala as forming a functionally important circuit for suppressing appetite. Using genetically encoded anatomical, optogenetic 8 and pharmacogenetic 9 tools, we demonstrate that activation of these neurons projecting to the central nucleus of the amygdala suppresses appetite. In contrast, inhibition of these neuron