title: CA1 pyramidal cell theta-burst firing triggers endocannabinoid-mediated long-term depression at both somatic and dendritic inhibitory synapses.
abstract: Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term synaptic depression of neurotransmitter release throughout the brain. Short-term depression is typically triggered by postsynaptic, depolarization-induced calcium rises, whereas long-term depression is induced by synaptic activation of Gq/11 protein-coupled receptors. Here we report that a physiologically relevant pattern of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal CA1 pyramidal neurons, can trigger long-term depression of inhibitory transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1 interneurons and pyramidal cells, followed by post hoc morphological reconstructions of the interneurons' axon, revealed that somatic and dendritic inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous recordings from neighboring pyramidal cells demonstrated that eCB signaling triggered by TBF was highly restricted to only a single, active cell. Furthermore, pairing submaximal endogenous activation of metabotropic glutamate or muscarinic acetylcholine receptors with submaximal TBF unmasked associative iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory terminals, long-term plasticity under various recording conditions was spared at these synapses. Consistent with this observation, TBF also shifted the balance of excitation and inhibition in favor of excitatory throughput, thereby altering information flow through the CA1 circuit. Given the near ubiquity of burst-firing activity patterns and CB1R expression in the brain, the properties described here may be a general means by which neurons fine tune the strength of their inputs in a cell-wide and cell-specific manner.
authors: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Thomas J
authors: TJ
authors: Younts
authors: Vivien
authors: V
authors: Chevaleyre
authors: Pablo E
authors: PE
authors: Castillo
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D063388:Endocannabinoids / Q000494:pharmacology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*; D013826:Theta Rhythm / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D018683:Excitatory Amino Acid Agents; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251
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