title: Tonic and transient endocannabinoid regulation of AMPAergic miniature postsynaptic currents and homeostatic plasticity in embryonic motor networks.
abstract: Endocannabinoid signaling has been shown to mediate synaptic plasticity by retrogradely inhibiting presynaptic transmitter release in several systems. We found that endocannabinoids act tonically to regulate AMPA miniature postsynaptic current (mPSC) frequency in embryonic motor circuits of the chick spinal cord. Further, strong postsynaptic depolarizations also induced a short-lived endocannabinoid-mediated suppression of mEPSC frequency. Unlike many previous studies, endocannabinoid signaling was not found to influence evoked transmitter release. The results suggest a special role for spontaneous glutamatergic mPSCs and their control by endocannabinoids in the developing spinal cord. We determined that blocking endocannabinoid signaling, which increases spontaneous glutamatergic release, increased spontaneous network activity in vitro and in vivo. Previous work in spinal motoneurons had shown that reducing spontaneous network activity (SNA) chronically in vivo led to homeostatic increases in AMPA and GABA mPSC amplitude (homeostatic synaptic plasticity). Blocking endocannabinoid signaling in vivo, and thus increasing SNA, triggered compensatory decreases of both AMPA and GABA mPSC amplitudes. These findings, combined with previous results, are consistent with the idea that this form of homeostatic synaptic plasticity is a bidirectional process in the living embryo. Together, our results suggest a role for tonic signaling of endocannabinoids as a potential mechanism to regulate the level of SNA, which is known to be critical for synaptic maturation in the embryonic spinal cord.
authors.affiliation: Department of Physiology, Emory University, School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez-Islas
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Garcia-Bereguiain
authors.forename: Peter
authors.initials: P
authors.lastname: Wenner
mesh_terms: D000367:Age Factors; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D002642:Chick Embryo; D004558:Electric Stimulation / Q000379:methods; D063388:Endocannabinoids / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology*; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D048588:Benzoxazines; D063388:Endocannabinoids; D018690:Excitatory Amino Acid Agonists; D006573:Heterocyclic Compounds, 1-Ring; C522826:LY2183240; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D005680:gamma-Aminobutyric Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D014508:Urea; C107594:N-(4-hydroxyphenyl)arachidonylamide