title: Endocannabinoid-dependent long-term depression in a nociceptive synapse requires coordinated presynaptic and postsynaptic transcription and translation.
abstract: Endocannabinoids (eCBs) play an important role in long-term regulation of synaptic signaling in both vertebrates and invertebrates. In this study, the role of transcription- and translation-dependent processes in presynaptic versus postsynaptic neurons was examined during eCB-mediated synaptic plasticity in the CNS of the leech. Low-frequency stimulation (LFS) of non-nociceptive afferents elicits eCB-dependent long-term depression (eCB-LTD) heterosynaptically in nociceptive synapses that lasts at least 2 h. Bath application of emetine, a protein synthesis inhibitor, blocked eCB-LTD after afferent LFS or exogenous eCB application, indicating that this depression was translation dependent. Bath application of actinomycin D, an irreversible RNA synthesis inhibitor, or 5,6-dichlorobenzimidazole 1-β-d-ribofurandoside (DRB), a reversible RNA synthesis inhibitor, also prevented eCB-LTD. Selective injection of DRB or emetine into the presynaptic or postsynaptic neuron before LFS indicated that eCB-LTD required transcription and translation in the postsynaptic neuron but only translation in the presynaptic cell. Depression observed immediately after LFS was also blocked when these transcription- and translation-dependent processes were inhibited. It is proposed that induction of eCB-LTD in this nociceptive synapse requires the coordination of presynaptic protein synthesis and postsynaptic mRNA and protein synthesis. These findings provide significant insights into both eCB-based synaptic plasticity and understanding how activity in non-nociceptive afferents modulates nociceptive pathways.
authors: Division of Basic Biomedical Sciences, Neuroscience Group, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota 57069 USA.
authors: Sharleen
authors: S
authors: Yuan
authors: Brian D
authors: BD
authors: Burrell
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001703:Biophysics; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004558:Electric Stimulation; D063388:Endocannabinoids / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007865:Leeches; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D009415:Nerve Net / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000187:drug effects*; D013997:Time Factors
chemical_list: C446284:5,6-dibromo-1,2-dimethylgramine; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D007211:Indoles; D003609:Dactinomycin; C094503:glyceryl 2-arachidonate