title: Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells.
abstract: The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlation with synaptic LTP induction. Because it is not possible to block NMDA spikes pharmacologically while maintaining NMDA receptors available to initiate synaptic plasticity, it remains unclear whether NMDA spikes alone can trigger LTP. Here we use dendritic recordings and calcium imaging to analyse the role of NMDA spikes in associative LTP in CA3 pyramidal cells. We show that NMDA spikes produce regenerative branch-specific calcium transients. Decreasing the probability of NMDA spikes reduces LTP, whereas increasing their probability enhances LTP. NMDA spikes and LTP occur without back-propagating action potentials. However, action potentials can facilitate LTP induction by promoting NMDA spikes. Thus, NMDA spikes are necessary and sufficient to produce the critical postsynaptic depolarization required for associative LTP in CA3 pyramidal cells.
authors.affiliation: Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, ETH Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Brandalise
authors.affiliation: Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, ETH Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Carta
authors.affiliation: Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, ETH Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Fritjof
authors.initials: F
authors.lastname: Helmchen
authors.affiliation: Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02453, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lisman
authors.affiliation: Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, ETH Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Gerber
mesh_terms: D000200:Action Potentials; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D017774:Long-Term Potentiation; D016202:N-Methylaspartate / Q000378:metabolism*; D009473:Neuronal Plasticity; D011336:Probability; D017966:Pyramidal Cells / Q000378:metabolism*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D002118:Calcium