Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression

Sadegh Nabavi, Helmut W. Kessels, Stephanie Alfonso, Jonathan Aow, Rocky Fox, Roberto Malinow

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

NMDA receptor (NMDAR) activation controls long-term potentiation (LTP) as well as long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. A long-standing view proposes that a high level of Ca(2+) entry through NMDARs triggers LTP; lower Ca(2+) entry triggers LTD. Here we show that ligand binding to NMDARs is sufficient to induce LTD; neither ion flow through NMDARs nor Ca(2+) rise is required. However, basal levels of Ca(2+) are permissively required. Lowering, but not maintaining, basal Ca(2+) levels with Ca(2+) chelators blocks LTD and drives strong synaptic potentiation, indicating that basal Ca(2+) levels control NMDAR-dependent LTD and basal synaptic transmission. Our findings indicate that metabotropic actions of NMDARs can weaken active synapses without raising postsynaptic calcium, thereby revising and expanding the mechanisms controlling synaptic plasticity
Original languageEnglish
Pages (from-to)4027-4032
JournalPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume110
Issue number10
DOIs
Publication statusPublished - 2013

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