Document Detail

Endocannabinoids gate state-dependent plasticity of synaptic inhibition in feeding circuits.
MedLine Citation:
PMID:  21835348     Owner:  NLM     Status:  MEDLINE    
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.
Karen M Crosby; Wataru Inoue; Quentin J Pittman; Jaideep S Bains
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuron     Volume:  71     ISSN:  1097-4199     ISO Abbreviation:  Neuron     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-12     Completed Date:  2011-10-18     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  8809320     Medline TA:  Neuron     Country:  United States    
Other Details:
Languages:  eng     Pagination:  529-41     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Hotchkiss Brain Institute and Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N4N1, Canada.
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MeSH Terms
Adrenal Cortex Hormones / physiology
Cannabinoid Receptor Modulators / physiology*
Food Deprivation / physiology*
Hypothalamus / physiology
Long-Term Potentiation / drug effects,  physiology
Long-Term Synaptic Depression / physiology
Neural Inhibition / physiology*
Neuronal Plasticity / physiology*
Nitric Oxide / physiology
Patch-Clamp Techniques / methods
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 / agonists,  antagonists & inhibitors,  physiology*
Receptors, N-Methyl-D-Aspartate / physiology
Satiation / physiology*
gamma-Aminobutyric Acid / metabolism,  physiology
Grant Support
15116//Canadian Institutes of Health Research; //Canadian Institutes of Health Research
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Cannabinoid Receptor Modulators; 0/Endocannabinoids; 0/Receptor, Cannabinoid, CB1; 0/Receptors, N-Methyl-D-Aspartate; 10102-43-9/Nitric Oxide; 56-12-2/gamma-Aminobutyric Acid
Comment In:
Neuron. 2011 Aug 11;71(3):385-7   [PMID:  21835336 ]

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