title: Endocannabinoids gate state-dependent plasticity of synaptic inhibition in feeding circuits.
abstract: Changes in food availability alter the output of hypothalamic nuclei that underlie energy homeostasis. Here, we asked whether food deprivation impacts the ability of GABA synapses in the dorsomedial hypothalamus (DMH), an important integrator of satiety signals, to undergo activity-dependent changes. GABA synapses in DMH slices from satiated rats exhibit endocannabinoid-mediated long-term depression (LTD(GABA)) in response to high-frequency stimulation of afferents. When CB1Rs are blocked, however, the same stimulation elicits long-term potentiation (LTP(GABA)), which manifests presynaptically and requires heterosynaptic recruitment of NMDARs and nitric oxide (NO). Interestingly, NO signaling is required for eCB-mediated LTD(GABA). Twenty-four hour food deprivation results in a CORT-mediated loss of CB1R signaling and, consequently, GABA synapses only exhibit LTP(GABA). These observations indicate that CB1R signaling promotes LTD(GABA) and gates LTP(GABA). Furthermore, the satiety state of an animal, through regulation of eCB signaling, determines the polarity of activity-dependent plasticity at GABA synapses in the DMH.
authors.affiliation: Hotchkiss Brain Institute and Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N4N1, Canada.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Crosby
authors.forename: Wataru
authors.initials: W
authors.lastname: Inoue
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Pittman
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
mesh_terms: D000305:Adrenal Cortex Hormones / Q000502:physiology; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D063388:Endocannabinoids; D005508:Food Deprivation / Q000502:physiology*; D007031:Hypothalamus / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012527:Satiation / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology
chemical_list: D000305:Adrenal Cortex Hormones; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid