Increasing Ca2+ transients by broadening postsynaptic action potentials enhances timing-dependent synaptic depression

Yu Dong Zhou, Corey D. Acker, Theoden I. Netoff, Kamal Sen, John A. White

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Repeated induction of pre- and postsynaptic action potentials (APs) at a fixed time difference leads to long-term potentiation (LTP) or long-term depression (LTD) of the synapse, depending on the temporal order of pre- and postsynaptic activity. This phenomenon of spike-timing-dependent plasticity (STDP) is believed to arise by nonlinear processes that lead to larger calcium transients (and thus LTP) when presynaptic APs precede postsynaptic APs and smaller calcium transients (and thus LTD) when postsynaptic APs precede presynaptic APs. In contrast to predictions from such calcium-peak-detector models, we show that constitutively or artificially broadened APs in layer II/III pyramidal cells of entorhinal cortex (EC) lead to an increase in the dendritic calcium transient and shift the balance of STDP toward LTD. STDP in entorhinal pyramidal cells is NMDA-receptor-dependent and modulated by the Cav 1 Ca2+ channel-blocker nifedipine. Results are consistent with an elaboration of the calcium-peak-detector model in which downstream signals from voltage-dependent Ca2+ channels suppress LTP relative to LTD. Our results suggest that modulation of AP width is a potent way to adjust the rules of synaptic plasticity in the EC.

Original languageEnglish (US)
Pages (from-to)19121-19125
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - Dec 27 2005


  • Calcium imaging
  • Entorhinal cortex
  • NMDA receptors nifedipine
  • Spike-timing-dependent plasticity

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