Dynamic GABAergic afferent modulation of AgRP neurons

• Published in: Nature neuroscience Vol. 19; no. 12; pp. 1628 - 1635
• Main Authors: Garfield, Alastair S, Shah, Bhavik P, Burgess, Christian R, Li, Monica M, Li, Chia, Steger, Jennifer S, Madara, Joseph C, Campbell, John N, Kroeger, Daniel, Scammell, Thomas E, Tannous, Bakhos A, Myers, Martin G, Andermann, Mark L, Krashes, Michael J, Lowell, Bradford B
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-12-2016; Nature Publishing Group
• Subjects: 13/1; 631/378/1488; 631/378/1488/1562; 64/60; 9/74; Agouti-Related Protein - metabolism; Animal Genetics and Genomics; Animals; Arcuate Nucleus of Hypothalamus - metabolism; Behavioral Sciences; Biological Techniques; Biomedicine; Diabetes; Endocrinology; Feeding Behavior; Food; GABA; GABAergic Neurons - metabolism; Hypothalamus; Medical examination; Medical schools; Mice; Neural circuitry; Neurobiology; Neurons; Neuropeptide Y - metabolism; Neurosciences; Observations; Physiology; Properties; Receptors, Leptin - metabolism; Sensation - physiology; Ann Arbor Michigan; United States > US; Maryland; Massachusetts; Michigan
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4392

AgRP neurons of the arcuate nucleus of the hypothalamus promote homeostatic feeding yet are rapidly suppressed by food-related sensory cues. The authors identify a population of inhibitory DMH-LepR neurons that relays real-time information about the nature and availability of food to dynamically modulate ARC-AgRP neuron activity and feeding behavior.
Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues before ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the preconsummatory modulation of ARC
AgRP
neurons. In a manner reciprocal to ARC
AgRP
neurons, ARC-projecting leptin receptor-expressing GABAergic vDMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, leptin receptor-expressing GABAergic vDMH neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARC
AgRP
neuron activity and feeding behavior.