title: Increasing Ca2+ transients by broadening postsynaptic action potentials enhances timing-dependent synaptic depression.
abstract: 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 Ca(V)1Ca(2+) channel-blocker nifedipine. Results are consistent with an elaboration of the calcium-peak-detector model in which downstream signals from voltage-dependent Ca(2+) 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.
authors.affiliation: Department of Biomedical Engineering, Center for Biodynamics, Center for Memory and Brain, Boston University, Boston, MA 02215, USA.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Zhou
authors.forename: Corey D
authors.initials: CD
authors.lastname: Acker
authors.forename: Theoden I
authors.initials: TI
authors.lastname: Netoff
authors.forename: Kamal
authors.initials: K
authors.lastname: Sen
authors.forename: John A
authors.initials: JA
authors.lastname: White
mesh_terms: D000200:Action Potentials; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003712:Dendrites / Q000473:pathology; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000473:pathology*; D019706:Excitatory Postsynaptic Potentials; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D017774:Long-Term Potentiation; D008954:Models, Biological; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D013569:Synapses / Q000502:physiology*; D013696:Temperature; D013997:Time Factors
chemical_list: D009543:Nifedipine; D002118:Calcium