title: Overnight fasting regulates inhibitory tone to cholinergic neurons of the dorsomedial nucleus of the hypothalamus.
abstract: The dorsomedial nucleus of the hypothalamus (DMH) contributes to the regulation of overall energy homeostasis by modulating energy intake as well as energy expenditure. Despite the importance of the DMH in the control of energy balance, DMH-specific genetic markers or neuronal subtypes are poorly defined. Here we demonstrate the presence of cholinergic neurons in the DMH using genetically modified mice that express enhanced green florescent protein (eGFP) selectively in choline acetyltransferase (Chat)-neurons. Overnight food deprivation increases the activity of DMH cholinergic neurons, as shown by induction of fos protein and a significant shift in the baseline resting membrane potential. DMH cholinergic neurons receive both glutamatergic and GABAergic synaptic input, but the activation of these neurons by an overnight fast is due entirely to decreased inhibitory tone. The decreased inhibition is associated with decreased frequency and amplitude of GABAergic synaptic currents in the cholinergic DMH neurons, while glutamatergic synaptic transmission is not altered. As neither the frequency nor amplitude of miniature GABAergic or glutamatergic postsynaptic currents is affected by overnight food deprivation, the fasting-induced decrease in inhibitory tone to cholinergic neurons is dependent on superthreshold activity of GABAergic inputs. This study reveals that cholinergic neurons in the DMH readily sense the availability of nutrients and respond to overnight fasting via decreased GABAergic inhibitory tone. As such, altered synaptic as well as neuronal activity of DMH cholinergic neurons may play a critical role in the regulation of overall energy homeostasis.
authors.affiliation: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Florian
authors.initials: F
authors.lastname: Groessl
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: David A
authors.initials: DA
authors.lastname: Talmage
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Role
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Jo
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000166:cytology / Q000502:physiology*; D004302:Dorsomedial Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005215:Fasting; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D018079:Receptors, GABA / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase