The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus
Open accessAbstract
Balanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrate that the presence of CB1 receptors in glutamatergic hippocampal neurons is both necessary and sufficient to provide substantial endogenous protection against kainic acid (KA)-induced seizures. The direct endocannabinoid-mediated control of hippocampal glutamatergic neurotransmission may constitute a promising therapeutic target for the treatment of disorders associated with excessive excitatory neuronal activity.
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A subset of embryonic cardinal type markers from the mouse dataset, including Mef2c, was also differentially expressed in adult human interneurons.
“we found that a subset of embryonic cardinal type markers from our mouse dataset (including Mef2c) was also differentially expressed in adult human interneurons”
From Developmental diversification of cortical inhibitory interneurons (2018) · cites this paper as [30]
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Canduela, M.-J., Mendizabal-Zubiaga, J., Puente, N., Reguero, L., Elezgarai, I., Ramos-Uriarte, A., Gerrikagoitia, I., & Grandes, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119401 · Cited by 13 · see citing works
- Authors
- Monory, K., Massa, F., Egertová, M., Eder, M., Blaudzun, H., Westenbroek, R., Kelsch, W., Jacob, W., Marsch, R., Ekker, M., Long, J., Rubenstein, J. L., Goebbels, S., Nave, K.-A., During, M., Klugmann, M., Wölfel, B., Dodt, H.-U., Zieglgänsberger, W., Wotjak, C. T., Mackie, K., Elphick, M. R., Marsicano, G., & Lutz, B.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Queen Mary University of London (GB)
- Max Planck Society (DE)
- Max Planck Institute of Psychiatry (DE)
- University of Washington (US)
- University of Ottawa (CA)
- University of California, San Francisco (US)
- Max Planck Institute of Experimental Medicine (DE)
- University of Auckland (NZ)
- Corresponding author
- Marsicano, Giovanni
- Lutz, Beat
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 51
- Issue
- 4
- Pages
- 455-466
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC1769341
- OpenAlex
- W2020808135
- Cited by
- 706
- References
- 65
- Citations by year
- 2026: 9 · 2025: 27 · 2024: 27 · 2023: 27 · 2022: 31 · 2021: 35 · 2020: 42 · 2019: 40 · 2018: 31 · 2017: 48 · 2016: 50 · 2015: 50 · 2014: 41 · 2013: 20 · 2012: 42
- FWCI
- 24.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2542 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health (5p01da015916-05)
- Biotechnology and Biological Sciences Research Council (S19916)
- National Institute of Mental Health (MH49428, MH065670, K05MH065670, R01MH049428, R37MH049428)
- National Institute on Drug Abuse (DA00286, DA11322, R01DA011322, K02DA000286, P01-DA015916, DA15916)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- endocannabinoid system, CB1 receptor, hippocampus, glutamatergic neurons, epileptogenesis, epileptiform seizures, kainic acid-induced seizures, VGLUT1, neuronal excitability, GABAergic neurons, seizure protection
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Calcium Channel Blockers, Epilepsy, gamma-Aminobutyric Acid, Hippocampus, Kainic Acid, Male, Membrane Potentials, Mice, Inbred C57BL, Mice, Transgenic, Morpholines, Naphthalenes, Nerve Net, Gene Expression, Calcium-Calmodulin-Dependent Protein Kinases, Pyramidal Cells, Glutamic Acid, Reverse Transcriptase Polymerase Chain Reaction, Receptor, Cannabinoid, CB1, Benzoxazines, Vesicular Glutamate Transport Protein 1, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cannabinoid Receptor Modulators, Endocannabinoids
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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.
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