title: Sustained firing of cartwheel cells in the dorsal cochlear nucleus evokes endocannabinoid release and retrograde suppression of parallel fiber synapses.
abstract: Neurons in many brain regions release endocannabinoids from their dendrites that act as retrograde signals to transiently suppress neurotransmitter release from presynaptic terminals. Little is known, however, about the physiological mechanisms of short-term endocannabinoid-mediated plasticity under physiological conditions. Here we investigate calcium-dependent endocannabinoid release from cartwheel cells (CWCs) of the mouse dorsal cochlear nucleus (DCN) in the auditory brainstem that provide feedforward inhibition onto DCN principal neurons. We report that sustained action potential firing by CWCs evokes endocannabinoid release in response to submicromolar elevation of dendritic calcium that transiently suppresses their parallel fiber (PF) inputs by >70%. Basal spontaneous CWC firing rates are insufficient to evoke tonic suppression of PF synapses. However, elevating CWC firing rates by stimulating PFs triggers the release of endocannabinoids and heterosynaptic suppression of PF inputs. Spike-evoked suppression by endocannabinoids selectively suppresses excitatory synapses, but glycinergic/GABAergic inputs onto CWCs are not affected. Our findings demonstrate a mechanism of transient plasticity mediated by endocannabinoids that heterosynaptically suppresses subsets of excitatory presynaptic inputs to CWCs that regulates feedforward inhibition of DCN principal neurons and may influence the output of the DCN.
authors: Section on Synaptic Transmission, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Miloslav
authors: M
authors: Sedlacek
authors: Philip W
authors: PW
authors: Tipton
authors: Stephan D
authors: SD
authors: Brenowitz
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D017626:Cochlear Nucleus / Q000166:cytology*; D003712:Dendrites / Q000378:metabolism; D004558:Electric Stimulation; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D002118:Calcium; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004963:Estrenes; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D010880:Piperidines; D011720:Pyrazoles; D011760:Pyrrolidinones; D011810:Quinoxalines; D013779:Tetrodotoxin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C103505:AM 251; C056723:FG 9041