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Multiple Functions of Endocannabinoid Signaling in the Brain
Open accessAbstract
Despite being regarded as a hippie science for decades, cannabinoid research has finally found its well-deserved position in mainstream neuroscience. A series of groundbreaking discoveries revealed that endocannabinoid molecules are as widespread and important as conventional neurotransmitters such as glutamate or GABA, yet they act in profoundly unconventional ways. We aim to illustrate how uncovering the molecular, anatomical, and physiological characteristics of endocannabinoid signaling has revealed new mechanistic insights into several fundamental phenomena in synaptic physiology. First, we summarize unexpected advances in the molecular complexity of biogenesis and inactivation of the two endocannabinoids, anandamide and 2-arachidonoylglycerol. Then, we show how these new metabolic routes are integrated into well-known intracellular signaling pathways. These endocannabinoid-producing signalosomes operate in phasic and tonic modes, thereby differentially governing homeostatic, short-term, and long-term synaptic plasticity throughout the brain. Finally, we discuss how cell type– and synapse-specific refinement of endocannabinoid signaling may explain the characteristic behavioral effects of cannabinoids.
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“It is widely accepted28 that CCK-positive cells in the rodent show selectively high expression of cannabinoid receptors and are involved in perisomatic inhibition.”
From Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (2018) · cites this paper as [28]
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Metadata
- Authors
- Katona, I., & Freund, T. F.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2012-07-21
- Volume
- 35
- Issue
- 1
- Pages
- 529-558
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC4273654
- OpenAlex
- W2168499817
- Cited by
- 630
- References
- 183
- Citations by year
- 2026: 39 · 2025: 35 · 2024: 29 · 2023: 44 · 2022: 53 · 2021: 60 · 2020: 56 · 2019: 32 · 2018: 50 · 2017: 57 · 2016: 34 · 2015: 45 · 2014: 43 · 2013: 41 · 2012: 11
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (090946)
- National Institute of Mental Health (R01MH054671, MH54671)
- National Institute of Neurological Disorders and Stroke (R37NS030549, R01NS030549, NS30549)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- endocannabinoid signaling, anandamide, 2-arachidonoylglycerol, signalosome, synaptic plasticity, intracellular signaling, cell type-specific signaling, brain
- MeSH terms
- Animals, Arachidonic Acids, Behavior, Animal, Brain, Glycerides, Humans, Ligands, Models, Neurological, Synaptic Transmission, Neuronal Plasticity, Signal Transduction, Receptors, Cannabinoid, Polyunsaturated Alkamides, Endocannabinoids
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