Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons: distinctive sufficiency for hippocampus-dependent and amygdala-dependent synaptic and behavioral functions
Open accessAbstract
A major goal in current neuroscience is to understand the causal links connecting protein functions, neural activity, and behavior. The cannabinoid CB1 receptor is expressed in different neuronal subpopulations, and is engaged in fine-tuning excitatory and inhibitory neurotransmission. Studies using conditional knock-out mice revealed necessary roles of CB1 receptor expressed in dorsal telencephalic glutamatergic neurons in synaptic plasticity and behavior, but whether this expression is also sufficient for brain functions is still to be determined. We applied a genetic strategy to reconstitute full wild-type CB1 receptor functions exclusively in dorsal telencephalic glutamatergic neurons and investigated endocannabinoid-dependent synaptic processes and behavior. Using this approach, we partly restored the phenotype of global CB1 receptor deletion in anxiety-like behaviors and fully restored hippocampus-dependent neuroprotection from chemically induced epileptiform seizures. These features coincided with a rescued hippocampal depolarization-induced suppression of excitation (DSE), a CB1 receptor-dependent form of synaptic plasticity at glutamatergic neurons. By comparison, the rescue of the CB1 receptor on dorsal telencephalic glutamatergic neurons prolonged the time course of DSE in the amygdala, and impaired fear extinction in auditory fear conditioning. These data reveal that CB1 receptor in dorsal telencephalic glutamatergic neurons plays a sufficient role to control neuronal functions that are in large part hippocampus-dependent, while it is insufficient for proper amygdala functions, suggesting an unexpectedly complex circuit regulation by endocannabinoid signaling in the amygdala. Our data pave the way to a better understanding of neuronal networks in the context of behavior, by fine-tuned interference with synaptic transmission processes.
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Functional expression of TRPV1 may be underestimated if TRPV1 is expressed post- and presynaptically and acts far away from its synthesis sites.
“functional expression may be underestimated if TRPV1 is expressed post and presynaptically (Aguiar et al., 2014) and acts far away from its synthesis sites (Gutierrez-Rodriguez et al., 2016; Ruehle et al., 2013).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Ruehle et al., 2013
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- Authors
- Ruehle, S., Remmers, F., Romo-Parra, H., Massa, F., Wickert, M., Wortge, S., Haring, M., Kaiser, N., Marsicano, G., Pape, H.-C., & Lutz, B.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Inserm (FR)
- University of Münster (DE)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-06-19
- Volume
- 33
- Issue
- 25
- Pages
- 10264-10277
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6618598
- OpenAlex
- W2066134510
- Cited by
- 132
- References
- 52
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 3 · 2023: 6 · 2022: 12 · 2021: 16 · 2020: 15 · 2019: 8 · 2018: 10 · 2017: 12 · 2016: 12 · 2015: 15 · 2014: 7 · 2013: 2
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Subproject A04, TRR‐58, SFB TRR 58)
- Institut National de la Santé et de la Recherche Médicale
- FP7 Ideas: European Research Council (260515)
- 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 › Memory and Neural Mechanisms
- Keywords
- CB1 receptor, endocannabinoid signaling, synaptic plasticity, anxiety-like behavior, fear extinction, auditory fear conditioning, epileptiform seizures, neuroprotection
- MeSH terms
- Amygdala, Animals, Anxiety, Behavior, Animal, Hippocampus, Immunohistochemistry, Kainic Acid, Light, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, RNA, Synapses, Telencephalon, Blotting, Western, Mice, Knockout, Excitatory Amino Acid Agonists, Glutamic Acid, Receptor, Cannabinoid, CB1, Mice, Electrophysiological Phenomena, Real-Time Polymerase Chain Reaction
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