title: GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression.
abstract: Tetanus-induced heterosynaptic depression in the hippocampus is a key cellular mechanism in neural networks implicated in learning and memory. A growing body of evidence indicates that glial cells are important modulators of synaptic functions, but very little is known about their role in heterosynaptic plasticity. We examined the role of glial cells in heterosynaptic depression, knowing that tetanization and NMDA application caused depression of synaptic field responses (fEPSPs) and induced Ca2+ rise in glial cells. Here we report that chelating Ca2+ in a glial syncytium interfered with heterosynaptic depression and NMDA-induced fEPSP depression, suggesting that Ca2+ activation of glial cells is necessary for heterosynaptic depression. The NMDA-induced Ca2+ rise in glial cells was sensitive to tetrodotoxin and reduced by the GABAB antagonist CGP55845. Both heterosynaptic depression and simultaneous Ca2+ activation of glial cells were prevented by CGP55845, suggesting an involvement of the GABAergic network in glial activation and heterosynaptic depression. Also, the GABAB agonist baclofen caused both a Ca2+ rise in glial cells and fEPSP depression. Heterosynaptic depression, as well as NMDA- and baclofen-induced depression, were attenuated by an A1 antagonist, cyclopentyl-theophylline, whereas glial cell activation was not, indicating a role of adenosine downstream of glial activation. Finally, heterosynaptic depression requires ATP degradation because ectonucleotidase inhibitors reduced this plasticity. Our work indicates that Ca2+ activation of glial cells is necessary for heterosynaptic depression, which involves the sequential interaction of Schaffer collaterals, the GABAergic network, and glia. Thus, glial and neuronal networks are functionally associated during the genesis of heterosynaptic plasticity at mammalian central excitatory synapses.
authors.affiliation: Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Serrano
authors.forename: Nasser
authors.initials: N
authors.lastname: Haddjeri
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lacaille
authors.forename: Richard
authors.initials: R
authors.lastname: Robitaille
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D043682:Receptor, Adenosine A1; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D002118:Calcium