Role of endogenous cannabinoids in synaptic signaling.

By Tamás F. Freund, I. Katona, Daniele Piomelli. Physiological Reviews, 2003

1,603 citations recorded by the source corpus.

Research of cannabinoid actions was boosted in the 1990s by remarkable discoveries including identification of endogenous compounds with cannabimimetic activity (endocannabinoids) and the cloning of their molecular targets, the CB1 and CB2 receptors. Although the existence of an endogenous cannabinoid signaling system has been established for a decade, its physiological roles have just begun to unfold. In addition, the behavioral effects of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, the major active compound of hashish and marijuana, await explanation at the cellular and network levels. Recent physiological, pharmacological, and high-resolution anatomical studies provided evidence that the major physiological effect of cannabinoids is the regulation of neurotransmitter release via activation of presynaptic CB1 receptors located on distinct types of axon terminals throughout the brain. Subsequent discoveries shed light on the functional consequences of this localization by demonstrating the involvement of endocannabinoids in retrograde signaling at GABAergic and glutamatergic synapses. In this review, we aim to synthesize recent progress in our understanding of the physiological roles of endocannabinoids in the brain. First, the synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. The fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release. Finally, the possible functions of endocannabinoids as retrograde synaptic signal molecules are discussed in relation to synaptic plasticity and network activity patterns.

Subfields: Cellular and Molecular Neuroscience, Pharmacology

View Paper: https://www.semanticscholar.org/paper/f80a200d6ea3bb68a3d207ffe489bac2870837bd

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Citations in the corpus

The Endocannabinoid System as an Emerging Target of Pharmacotherapy (2006, background): “…both inhibitory GABAergic and excitatory glutamatergic transmissions via multiple mechanisms (Marsicano and Lutz, 1999; Alger, 2002, 2004; Gerdeman et al., 2002; Robbe et al., 2002; Azad et al., 2003; Freund et al., 2003; Gerdeman and Lovinger, 2003; Kim and Alger, 2004; Isokawa and Alger, 2005).”
Mammalian G proteins and their cell type specific functions. (2005, background): “Gq/G11-coupled receptors like group I mGluRs as well as muscarinic M1 receptors can lead to the activation of the retrogradely acting cannabinoid system by stimulating the formation of endocannabinoids (136, 189, 380, 409).”
Critical period plasticity in local cortical circuits (2005, background): “Indeed, infusion of cannabinoids, which primarily bind presynaptic CB1 receptors to reduce GABA releas”
Distinct coincidence detectors govern the corticostriatal spike timing‐dependent plasticity (2010, background): “Journal compilation C© 2010 The Physiological Society efficacy changes (Freund et al. 2003; Chevaleyre et al. 2006; Kano et al. 2009).”
The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis (2004, background): “The primary effect of cannabinoids is the modulation of neurotransmitter release via activation of presynaptic CB-1Rs (reviewed in Belue et al, 1995; Freund et al, 2003; Pertwee, 1999a).”
Endocannabinoid signaling as a synaptic circuit breaker in neurological disease (2008, background): “The CB 1 receptor is so abundant because it is found at nearly all types of central nervous system synapses, but, surprisingly, this receptor seems to consistently reside on the presynaptic side of the synaps”
Endocannabinoid signaling and synaptic function (2012, background): “Their role as retrograde messengers suppressing transmitter release in a transient or long-lasting manner, at both excitatory and inhibitory synapses, is now well established (Alger, 2012; Chevaleyre et al., 2006; Freund et al., 2003; Kano et al., 2009; Katona and Freund, 2012).”
The endocannabinoid system and its therapeutic exploitation (2004, neutral): “In particular, endocannabinoids in the CNS intervene in both short-term and long-term forms of synaptic plasticity, including depolarization-induced suppression of both excitatory and inhibitory neurotransmission, long-term potentiation and depression, and long-term depression of inhibitio”
Neural syntax: cell assemblies, synapsembles and readers (2010, neutral): “For example, drug activation of presynatic cannabinoid receptors (Freund et al., 2003) had no effect on the positional representation of hippocampal place cells, field size, or their population vector, thus leaving the ‘‘spatial map’’ intact, yet the rats could not solve a spatial task.”
The emerging role of the endocannabinoid system in endocrine regulation and energy balance. (2006, background): “They thus mediate a retrograde signal (30, 106, 107).”
Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning (2015, background): “Activation of cannabinoid receptor (Freund et al., 2003) reduces the probability of occurrence SPW-Rs in rats (Robbe et al., 2006) and mice (Maier et al., 2012; Sun et al., 2012) without affecting ripple frequency.”
Alcoholism: a systems approach from molecular physiology to addictive behavior. (2009, background): “, 2-arachidonyl-glycerol (2AG) and anandamide, their biosynthetic and inactivating enzymes and, perhaps, transporters for endocannabinoids (146).”
The endocannabinoid system controls key epileptogenic circuits in the hippocampus. (2006, neutral): “, 2003) and pharmacological effects of exogenous cannabinoids on GABA release (Freund et al., 2003).”
Distribution of cannabinoid receptors in the central and peripheral nervous system. (2005, background): “In contrast, CB1 receptor expression is relatively less in deeper layer III and layer V (Freund et al. 2003).”
Cannabinoid physiology and pharmacology: 30 years of progress. (2004, background): “1), including arachidonylethanolamide (anandamide), 2-arachidonoyl- glycerol (2-AG), and 2-arachidonylglycerylether (noladin ether) (see Di Marzo et al., 1999; Freund et al., 2003; Giuffrida et al., 2001; Howlett, 2002; Martin et al., 1999; Schmid, 2000; Sugiura and Waku, 2000 for review).”