title: Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons.
abstract: Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cembrowski
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Mensh
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Nelson
authors.initials: N
authors.lastname: Spruston
mesh_terms: D000200:Action Potentials; D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D017966:Pyramidal Cells / Q000502:physiology*; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
chemical_list: D012964:Sodium
keywords: CA1 pyramidal neuron; dendritic excitability; dendritic sodium spikes; long-term potentiation (LTP); neuroscience; perforant pathway; rat