Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses
Open accessAbstract
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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Tonic ECB signaling in the BLA and elsewhere is mediated by AEA, whereas phasic ECB responses to robust neuronal activation are sub-served by 2-AG.
“There is growing evidence that tonic ECB signaling in the BLA and elsewhere is mediated by AEA, whereas phasic ECB responses to robust neuronal activation are sub-served by 2-AG [53–56].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [54]
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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
- Published
- 2010-03-28
- Volume
- 13
- Issue
- 5
- Pages
- 592-600
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- 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 › 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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