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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Activity-dependent scaling of quantal amplitude in neocortical neurons
Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C., & Nelson, S. B. (1998) · Nature · doi:10.1038/36103 · Cited by 2,226
Endocannabinoid-Mediated Control of Synaptic Transmission
Kano, M., Ohno‐Shosaku, T., Hashimotodani, Y., Uchigashima, M., & Watanabe, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00019.2008 · Cited by 1,595
The self-tuning neuron: synaptic scaling of excitatory synapses
Turrigiano, G. G. (2008) · Cell · doi:10.1016/j.cell.2008.10.008 · Cited by 1,533
Katona, I., Sperlágh, B., Sı́k, A., Käfalvi, A., Vizi, E. S., Mackie, K., & Freund, T. F. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04544.1999 · Cited by 1,218
Marsicano, G., & Lutz, B. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00847.x · Cited by 937
Heterosynaptic LTD of Hippocampal GABAergic Synapses
Chevaleyre, V., & Castillo, P. E. (2003) · Neuron · doi:10.1016/s0896-6273(03)00235-6 · Cited by 647
Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids
Alger, B. E. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00080-1 · Cited by 616
Self-citationPresynaptic Specificity of Endocannabinoid Signaling in the Hippocampus
Wilson, R. I., Kunos, G., & Nicoll, R. A. (2001) · Neuron · doi:10.1016/s0896-6273(01)00372-5 · Cited by 543
Kawamura, Y., Fukaya, M., Maejima, T., Yoshida, T., Miura, E., Watanabe, M., Ohno‐Shosaku, T., & Kano, M. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4872-05.2006 · Cited by 511
Pharmacological Profile of the Selective FAAH Inhibitor KDS-4103 (URB597)
Piomelli, D., Tarzia, G., Duranti, A., Tontini, A., Mor, M., Compton, T. R., Dasse, O. A., Monaghan, E. P., Parrott, J. A., & Putman, D. (2006) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2006.00021.x · Cited by 451
Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation
Maffei, A., Nelson, S. B., & Turrigiano, G. G. (2004) · Nature Neuroscience · doi:10.1038/nn1351 · Cited by 415
Applicability of the coefficient of variation method for analyzing synaptic plasticity
Faber, D. S., & Korn, H. (1991) · Biophysical Journal · doi:10.1016/s0006-3495(91)82162-2 · Cited by 369
Kilman, V., van Rossum, M. C. W., & Turrigiano, G. G. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-04-01328.2002 · Cited by 362
Leung, D., Saghatelian, A., Simon, G. M., & Cravatt, B. F. (2006) · Biochemistry · doi:10.1021/bi060163l · Cited by 354
The endogenous cannabinoid system and brain development
Fernández‐Ruíz, J., Berrendero, F., Hernández, M., & Ramos, J. A. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01491-5 · Cited by 345
Kim, J., Isokawa, M., Ledent, C. A., & Alger, B. E. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-23-10182.2002 · Cited by 318
Self-citationInternalization and Recycling of the CB1 Cannabinoid Receptor
Hsieh, C., Brown, S. M., Derleth, C., & Mackie, K. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0730493.x · Cited by 296
Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus
Kim, J., & Alger, B. E. (2004) · Nature Neuroscience · doi:10.1038/nn1262 · Cited by 239
Self-citationSynaptic gain control and homeostasis
Burrone, J., & Murthy, V. N. (2003) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2003.09.007 · Cited by 236
Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus
Makara, J. K., Mor, M., Fegley, D., Szabó, S. I., Kathuria, S., Astarita, G., Duranti, A., Tontini, A., Tarzia, G., Rivara, S., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1521 · Cited by 235
Mechanisms of Endocannabinoid Inactivation: Biochemistry and Pharmacology
Giuffrida, A., Beltramo, M., & Piomelli, D. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29345-9 · Cited by 226
Distinct timing in the activity of cannabinoid-sensitive and cannabinoid-insensitive basket cells
Glickfeld, L. L., & Scanziani, M. (2006) · Nature Neuroscience · doi:10.1038/nn1688 · Cited by 222
Activity-dependent regulation of inhibitory synaptic transmission in hippocampal neurons
Hartman, K. N., Pal, S. K., Burrone, J., & Murthy, V. N. (2006) · Nature Neuroscience · doi:10.1038/nn1677 · Cited by 221
Poncer, J. C., McKinney, R. A., Gähwiler, B. H., & Thompson, S. M. (1997) · Neuron · doi:10.1016/s0896-6273(00)81246-5 · Cited by 207
Long-Term Plasticity of Endocannabinoid Signaling Induced by Developmental Febrile Seizures
Chen, K., Ratzliff, A., Hilgenberg, L. G. W., Gulyás, A. I., Freund, T. F., Smith, M., Dinh, T. P., Piomelli, D., Mackie, K., & Soltész, I. (2003) · Neuron · doi:10.1016/s0896-6273(03)00499-9 · Cited by 204
Cannabinoid Receptors and Their Role in Neuroprotection
van der Stelt, M., & Marzo, V. D. (2005) · NeuroMolecular Medicine · doi:10.1385/nmm:7:1-2:037 · Cited by 192
Neu, A. D., Földy, C., & Soltész, I. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.115691 · Cited by 190
Hashimotodani, Y., Ohno‐Shosaku, T., & Kano, M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4159-06.2007 · Cited by 186
Varvel, S. A., Wise, L. E., Niyuhire, F., Cravatt, B. F., & Lichtman, A. H. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301224 · Cited by 179
Houweling, A. R., Bazhenov, M., Timofeev, I., Steriade, M., & B, T. J. S. A. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh184 · Cited by 172
Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons
Losonczy, A., Biró, Á. A., & Nusser, Z. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0304752101 · Cited by 161
McKinney, R. A., Debanne, D., Gähwiler, B. H., & Thompson, S. M. (1997) · Nature Medicine · doi:10.1038/nm0997-990 · Cited by 157
Biosynthetic Pathways of the Endocannabinoid Anandamide
Okamoto, Y., Wang, J., Morishita, J., & Ueda, N. (2007) · Chemistry & Biodiversity · doi:10.1002/cbdv.200790155 · Cited by 147
Echegoyen, J., Neu, A., Graber, K. D., & Soltesz, I. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000700 · Cited by 146
Földy, C., Neu, A. D., Jones, M. V., & Soltész, I. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4587-05.2006 · Cited by 142
Kim, J., & Tsien, R. W. (2008) · Neuron · doi:10.1016/j.neuron.2008.05.009 · Cited by 124
Self-citationNyilas, R., Dudok, B., Urbán, G. M., Mackie, K., Watanabe, M., Cravatt, B. F., Freund, T. F., & Katona, I. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5102-07.2008 · Cited by 119
Cristino, L., Starowicz, K., De Petrocellis, L., Morishita, J., Ueda, N., Guglielmotti, V., & Di Marzo, V. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2007.11.047 · Cited by 115
Egertová, M., Simon, G. M., Cravatt, B. F., & Elphick, M. R. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21568 · Cited by 111
Luk, T., Jin, W., Zvonok, A. M., Lu, D., Lin, X., Chavkin, C., Makriyannis, A., & Mackie, K. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705792 · Cited by 99
Rinaldi, M. L., Duigou, A. L., Oustric, D., Barth, F., Bouaboula, M., Carayon, P., Casellas, P., & Fur, G. L. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37898-x · Cited by 98
Falenski, K. W., Blair, R. E., Sim‐Selley, L. J., Martin, B. R., & DeLorenzo, R. J. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.01.065 · Cited by 81
Fortin, D. A., Trettel, J., & Levine, E. S. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00351.2004 · Cited by 77
Differential Activity-Dependent, Homeostatic Plasticity of Two Neocortical Inhibitory Circuits
Bartley, A. F., Huang, Z. J., Huber, K. M., & Gibson, J. R. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90635.2008 · Cited by 72
Trasande, C. A., & Ramirez, J. (2007) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0b013e318033787f · Cited by 67
Bausch, S. B., He, S., Petrova, Y., Wang, X., & McNamara, J. O. (2006) · Journal of Neurophysiology · doi:10.1152/jn.00355.2006 · Cited by 50
Physiological roles of 2‐arachidonoylglycerol, an endogenous cannabinoid receptor ligand
Sugiura, T. (2009) · BioFactors · doi:10.1002/biof.18 · Cited by 40
Buckby, L. E., Jensen, T. P., Smith, P. J. E., & Empson, R. M. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.01.009 · Cited by 35
Bertrand, S. S., & Lacaille, J. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0369f.x · Cited by 34
Morozov, Y. M., Ben‐Ari, Y., & Freund, T. F. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03507.x · Cited by 33
Flagged first, then by citations
1 of the 51 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
