title: Astrocyte signaling controls spike timing-dependent depression at neocortical synapses.
abstract: Endocannabinoid mediated spike timing-dependent depression (t-LTD) is crucially involved in the development of the sensory neocortex. t-LTD at excitatory synapses in the developing rat barrel cortex requires cannabinoid CB(1) receptor (CB(1)R) activation, as well as activation of NMDA receptors located on the presynaptic terminal, but the exact signaling cascade leading to t-LTD remains unclear. We found that astrocytes are critically involved in t-LTD. Astrocytes gradually increased their Ca(2+) signaling specifically during the induction of t-LTD in a CB(1)R-dependent manner. In this way, astrocytes might act as a memory buffer for previous coincident neuronal activity. Following activation, astrocytes released glutamate, which activated presynaptic NMDA receptors to induce t-LTD. Astrocyte stimulation coincident with afferent activity resulted in long-term depression, indicating that astrocyte activation is sufficient for the induction of synaptic depression. Taken together, our findings describe the retrograde signaling cascade underlying neocortical t-LTD. The critical involvement of astrocytes in this process highlights their importance for experience-dependent sensory remodeling.
authors.affiliation: Department of Physiology, University of Berne, Berne, Switzerland.
authors.forename: Rogier
authors.initials: R
authors.lastname: Min
authors.forename: Thomas
authors.initials: T
authors.lastname: Nevian
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D048588:Benzoxazines / Q000494:pharmacology; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011336:Probability; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013779:Tetrodotoxin / Q000494:pharmacology; D013788:Thalamus / Q000166:cytology; D013997:Time Factors
chemical_list: D048588:Benzoxazines; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D026941:Sodium Channel Blockers; C103505:AM 251; D018698:Glutamic Acid; D013779:Tetrodotoxin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium