The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
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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“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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Activity-dependent scaling of quantal amplitude in neocortical neurons
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The self-tuning neuron: synaptic scaling of excitatory synapses
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Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids
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Self-citationPresynaptic Specificity of Endocannabinoid Signaling in the Hippocampus
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Pharmacological Profile of the Selective FAAH Inhibitor KDS-4103 (URB597)
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Endocannabinoid Signaling and Synaptic Function
Castillo, P. E., Younts, T. J., Chávez, A. E., & Hashimotodani, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.020 · Cited by 1,191
Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement
Turrigiano, G. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153238 · Cited by 671
Multiple Functions of Endocannabinoid Signaling in the Brain
Katona, I., & Freund, T. F. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150420 · Cited by 630
Endocannabinoid signalling in reward and addiction
Parsons, L. H., & Hurd, Y. L. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn4004 · Cited by 488
Ligresti, A., PETROCELLIS, L. D., & Marzo, V. D. (2016) · Physiological Reviews · doi:10.1152/physrev.00002.2016 · Cited by 505
Metadata
- 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 (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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