Cited by 149Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchNeural dynamics and brain function

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Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses

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Kim, Jimok, Alger, Bradley E·2010·Nature Neuroscience

DOI 10.1038/nn.2517PMC PMC2860695

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Abstract

When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. We found that, although a large population of inhibitory synapses was homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthened a subset of GABAergic synapses that express cannabinoid receptors. In rat hippocampal slice cultures, a 3-5-d blockade of neuronal firing facilitated uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augmented GABA release probability, fostering rapid depression of synaptic inhibition and on-demand disinhibition. This regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks.

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Authors: Kim, J., & Alger, B. E.
Affiliations: University of Maryland, Baltimore (US)
Corresponding author: Alger, Bradley E
ORCID: Alger, Bradley E
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2010-03-28
Volume: 13
Issue: 5
Pages: 592-600
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.2517
PMC: PMC2860695
OpenAlex: W1979518536
Cited by: 149
References: 51
Citations by year: 2026: 5 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 13 · 2014: 14 · 2013: 21 · 2012: 15
FWCI: 13.85
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R01MH077277)
National Institute on Drug Abuse (R01DA014625)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords: synaptic homeostasis, inhibitory synapses, GABAergic synapses, cannabinoid receptors, hippocampus, synaptic inhibition, disinhibition, activity-dependent synaptic plasticity
MeSH terms: Rimonabant, Animals, Arachidonic Acids, Benzamides, Biophysics, Calcium, Calcium Channel Blockers, Carbamates, Dose-Response Relationship, Drug, Drug Interactions, Electric Stimulation, Enzyme Inhibitors, gamma-Aminobutyric Acid, Glycerides, Hippocampus, Homeostasis, Morpholines, Naphthalenes, Nerve Net, Neural Inhibition, Neurons, Piperidines, Polyamines, Pyrazoles, Synapses, Tetrodotoxin, Down-Regulation, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Conotoxins, Sodium Channel Blockers, Receptor, Cannabinoid, CB1, Benzoxazines, Rats, Polyunsaturated Alkamides, Inhibitory Postsynaptic Potentials, Agatoxins, Cannabinoid Receptor Modulators, Endocannabinoids, In Vitro Techniques

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Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses

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