Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids.
Endocannabinoids are well established as inhibitors of chemical synaptic transmission via presynaptic activation of the cannabinoid type 1 receptor (CB1R). Contrasting this notion, we show that dendritic release of endocannabinoids mediates potentiation of synaptic transmission at mixed (electrical and chemical) synaptic contacts on the goldfish Mauthner cell. Remarkably, the observed enhancement was not restricted to the glutamatergic component of the synaptic response but also included a parallel increase in electrical transmission. This effect involved the activation of CB1 receptors and was indirectly mediated via the release of dopamine from nearby varicosities, which in turn led to potentiation of the synaptic response via a cAMP-dependent protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can potentiate synaptic transmission, and its functional roles include the regulation of gap junction-mediated electrical synapses. Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives.
Cachope
Roger
R
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Mackie
Ken
K
Triller
Antoine
A
O'Brien
John
J
Pereda
Alberto E
AE
D000704:Analysis of Variance; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000819:agonists / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D063388:Endocannabinoids; D005136:Eye Proteins / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006054:Goldfish; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D000077285:Rimonabant; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D017630:Connexins; D063388:Endocannabinoids; D005136:Eye Proteins; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018094:Receptors, Metabotropic Glutamate; C100585:connexin 35 protein, vertebrate; C104077:metabotropic glutamate receptor type 1; C103505:AM 251; D008734:Methoxyhydroxyphenylglycol; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D014446:Tyrosine 3-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D000077285:Rimonabant; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine