title: Fasting induces a large, leptin-dependent increase in the intrinsic action potential frequency of orexigenic arcuate nucleus neuropeptide Y/Agouti-related protein neurons.
abstract: The neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus are thought to promote feeding. Here, we demonstrate that feeding state in vivo, through a leptin-dependent process, induces large and persistent changes in the electrophysiological activity of these neurons as measured extracellularly in vitro. Consistent with an orexigenic role, fasting induced a 4-fold increase in the basal action potential frequency of NPY/AgRP neurons. Leptin, when injected into fasted wild-type mice, induced a dose- and time-dependent decrease in spike frequency, which approached fed levels 2-3 h post treatment. In leptin-deficient (lep(ob)/lep(ob)) and leptin receptor-deficient (lepr(db)/lepr(db)) mice, NPY/AgRP spike frequency was not significantly increased by fasting, and even in mutant mice fed ad libitum, spike frequency was at least as high as in fasted wild-type mice. All recordings included GABA(A) and ionotropic glutamate receptor antagonists, suggesting that expression of this modulation is potentially intrinsic and not synaptically dependent. Recorded neurons were unambiguously identified using NPY-Sapphire transgenic mice. This is a remarkably straightforward example of a very robust in vitro electrophysiogical effect produced by a simple behavioral manipulation, food restriction.
authors.affiliation: Vollum Institute and The Center for the Study of Weight Regulation and Associated Disorders, Oregon Health & Science University, Portland, Oregon 97239, USA. katakaha@aecom.yu.edu
authors.forename: Kanji A
authors.initials: KA
authors.lastname: Takahashi
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
mesh_terms: D000200:Action Potentials; D054369:Agouti-Related Protein; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005508:Food Deprivation; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D011506:Proteins