title: Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales.
abstract: Agouti-related-peptide (AgRP) neurons-interoceptive neurons in the arcuate nucleus of the hypothalamus (ARC)-are both necessary and sufficient for driving feeding behavior. To better understand the functional roles of AgRP neurons, we performed optetrode electrophysiological recordings from AgRP neurons in awake, behaving AgRP-IRES-Cre mice. In free-feeding mice, we observed a fivefold increase in AgRP neuron firing with mounting caloric deficit in afternoon vs morning recordings. In food-restricted mice, as food became available, AgRP neuron firing dropped, yet remained elevated as compared to firing in sated mice. The rapid drop in spiking activity of AgRP neurons at meal onset may reflect a termination of the drive to find food, while residual, persistent spiking may reflect a sustained drive to consume food. Moreover, nearby neurons inhibited by AgRP neuron photostimulation, likely including satiety-promoting pro-opiomelanocortin (POMC) neurons, demonstrated opposite changes in spiking. Finally, firing of ARC neurons was also rapidly modulated within seconds of individual licks for liquid food. These findings suggest novel roles for antagonistic AgRP and POMC neurons in the regulation of feeding behaviors across multiple timescales.
authors.affiliation: Department of Endocrinology, Beth Israel Deaconess Medical Center, Boston, United States.
authors.forename: Yael
authors.identifier: http://orcid.org/0000-0002-6356-5856
authors.initials: Y
authors.lastname: Mandelblat-Cerf
authors.affiliation: Department of Endocrinology, Beth Israel Deaconess Medical Center, Boston, United States.
authors.forename: Rohan N
authors.initials: RN
authors.lastname: Ramesh
authors.affiliation: Department of Endocrinology, Beth Israel Deaconess Medical Center, Boston, United States.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Burgess
authors.affiliation: Department of Endocrinology, Beth Israel Deaconess Medical Center, Boston, United States.
authors.forename: Paola
authors.initials: P
authors.lastname: Patella
authors.affiliation: Department of Endocrinology, Beth Israel Deaconess Medical Center, Boston, United States.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Beth Israel Deaconess Medical Center, Boston, United States.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.affiliation: Department of Endocrinology, Beth Israel Deaconess Medical Center, Boston, United States.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Andermann
mesh_terms: D000200:Action Potentials; D054369:Agouti-Related Protein / Q000032:analysis*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D005247:Feeding Behavior; D051379:Mice; D009474:Neurons / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000032:analysis*
chemical_list: D054369:Agouti-Related Protein; D011333:Pro-Opiomelanocortin
keywords: AgRP; POMC; arcuate; feeding; food cue; mouse; neuroscience; tetrode