title: Activation conditions for the induction of metabotropic glutamate receptor-dependent long-term depression in hippocampal CA1 pyramidal cells.
abstract: Two forms of homosynaptic long-term depression (LTD) are distinguished in hippocampal CA1 pyramidal cells, one which is NMDA receptor dependent and the other metabotropic glutamate receptor (mGluR) dependent. Although the molecular processes involved in mGluR-LTD are well characterized, the conditions of circuit activation required for its induction remain unclear. We show that mGluR-LTD cannot be induced in synaptically coupled CA3-CA1 pyramidal cell pairs. Experiments to address the underlying mechanisms indicate that, even when glutamate transporters are blocked, one presynaptic cell releases insufficient glutamate to evoke an mGluR-mediated current in a connected CA1 cell. These findings imply that extrasynaptic diffusion is not a limiting factor and are consistent with a sparse distribution of functional mGluRs in the dendritic tree of pyramidal cells. Thus, the discharge of multiple Schaffer collaterals to a targeted cell is necessary for mGluR-LTD. Our experiments indicate that approximately eight CA3 inputs to a CA1 pyramidal cell must be activated to induce mGluR-LTD.
authors.affiliation: Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Jeanne
authors.initials: J
authors.lastname: Ster
authors.forename: Urs
authors.initials: U
authors.lastname: Gerber
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid