The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

Tanimura, Akio; Yamazaki, Maya; Hashimotodani, Yuki; Uchigashima, Motokazu; Kawata, Shinya; Abe, Manabu; Kita, Yoshiaki; Hashimoto, Katsufumi; Shimizu, Takao; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu

doi:10.1016/j.neuron.2010.01.021

Cited by 426 publications

(549 citation statements)

References 49 publications

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“…DSE and DSI are not observed in DAGLa-knockout mice, indicating that 2-AG mediates these mechanisms of synaptic plasticity [18,19]. DAGLa is concentrated postsynaptically in dendritic spines that are apposed to CB 1 -expressing axon terminals [62], which is consistent with the notion that 2-AG is synthesized postsynaptically but acts presynaptically.…”

Section: Introduction To Endocannabinoid Signallingsupporting

confidence: 80%

“…A second DAGL that is related to DAGLa based on sequence similarity has been identified and is known as DAGLb [17]. However, while DAGLb can catalyse the formation of 2-AG in vitro [17], comparative analysis of the brain content of 2-AG in DAGLa-and DAGLbknockout mice indicates that the contribution of DAGLb to 2-AG biosynthesis in adult brain is much less significant compared with DAGLa [18,19]. 2-AG is inactivated by the enzyme monoacylglycerol lipase (MAGL), which cleaves 2-AG into arachidonic acid and glycerol [20][21][22].…”

Section: Introduction To Endocannabinoid Signallingmentioning

confidence: 99%

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The evolution and comparative neurobiology of endocannabinoid signalling

Elphick

2012

Phil. Trans. R. Soc. B

153

137

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CB 1 -and CB 2 -type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB 1 -type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB 1 /CB 2 -type receptors originated in a common ancestor of extant chordates, and in the sea squirt Ciona intestinalis a CB 1 / CB 2 -type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB 1 /CB 2 -type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB 1 /CB 2 -mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids.

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Section: Introduction To Endocannabinoid Signallingsupporting

confidence: 80%

Section: Introduction To Endocannabinoid Signallingmentioning

confidence: 99%

The evolution and comparative neurobiology of endocannabinoid signalling

Elphick

2012

Phil. Trans. R. Soc. B

153

137

View full text Add to dashboard Cite

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“…2-Arachidonoylglycerol (2-AG) and Narachidonoylethanolamine (AEA), 2 arachidonic acid derivatives, are the chief endocannabinoids in the brain; cerebellum CB 1 R are predominantly activated by 2-AG. An increase in the concentration of postsynaptic Ca 2+ either by entry via voltagegated Ca 2+ channels or activation of type 1 metabotropic glutamate receptors brings about the release of 2-AG synthesized from diacylglycerol, a reaction catalyzed by diacylglycerol lipase-alpha in Purkinje cells, with the overall effect of activation of presynaptic CB 1 R [52][53][54][55][56]. In addition, several studies have reported the high density of CB 1 Rs in striatum and the presence of AEA throughout the basal ganglia, in particular in the globus pallidus and substantia nigra [31,57,58].…”

Section: Cannabinoid Receptors and Signaling In Relations To Central mentioning

confidence: 99%

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

et al. 2015

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Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor.

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“…The CB 1 receptor is responsible for both DSI/DSE which can be induced by application of CB 1 receptor agonists and are blocked by CB 1 receptor antagonists (Ohno-Shosaku et al, 2002b;Wilson and Nicoll, 2001). Also, both DSI and DSE are mediated by 2-arachidonoylglycerol (2-AG), one of the main eCBs in hippocampus (Gao et al, 2010;Tanimura et al, 2010). While DSI and DSE have been shown to exhibit qualitatively similar behaviour, their quantitative characteristics differ.…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid-mediated short-term plasticity in hippocampus

Zachariou

Thul

2014

J Comput Neurosci

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Endocannabinoids modulate both excitatory and inhibitory neurotransmission in hippocampus via activation of pre-synaptic cannabinoid receptors. Here, we present a model for cannabinoid mediated shortterm depression of excitation (DSE) based on our recently developed model for the equivalent phenomenon of suppressing inhibition (DSI). Furthermore, we derive a simplified formulation of the calcium-mediated endocannabinoid synthesis that underlies short-term modulation of neurotransmission in hippocampus. The simplified model describes cannabinoid-mediated short-term modulation of both hippocampal inhibition and excitation and is ideally suited for large network studies. Moreover, the implementation of the simplified DSI/DSE model provides predictions on how both phenomena are modulated by the magnitude of the pre-synaptic cell's activity. In addition we demonstrate the role of DSE in shaping the post-synaptic cell's firing behaviour qualitatively and quantitatively in dependence on eCB availability and the pre-synaptic cell's activity. Finally, we explore under which conditions the combination of DSI and DSE can temporarily shift the fine balance between excitation and inhibition. This highlights a mechanism by which eCBs might act in a neuro-protective manner during high neural activity.

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The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

Cited by 426 publications

References 49 publications

The evolution and comparative neurobiology of endocannabinoid signalling

The evolution and comparative neurobiology of endocannabinoid signalling

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

Cannabinoid-mediated short-term plasticity in hippocampus

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