title: Dendritic Na+ current inactivation can increase cell excitability by delaying a somatic depolarizing afterpotential.
abstract: Many central neurons support active dendritic spike backpropagation mediated by voltage-gated currents. Active spikes in dendrites have been shown capable of providing feedback to the soma to influence somatic excitability and firing dynamics through a depolarizing afterpotential (DAP). In pyramidal cells of the electrosensory lobe of weakly electric fish, Na(+) spikes in dendrites undergo a frequency-dependent broadening that enhances the DAP to increase somatic firing frequency. We use a combination of dynamical analysis and electrophysiological recordings to demonstrate that spike broadening in dendrites is primarily caused by a cumulative inactivation of dendritic Na(+) current. We further show that a reduction in dendritic Na(+) current increases excitability by decreasing the interspike interval and promoting burst firing. This process arises when inactivation of dendritic Na(+) current shifts the latency of the dendritic spike to delay the arrival of the DAP sufficiently to increase its impact on somatic membrane potential despite a reduction in dendritic excitability. Furthermore, the relationship between dendritic Na(+) current density and somatic excitability is nonmonotonic, as intermediate levels of dendritic Na(+) current exert the greatest excitatory influence. These results reveal that temporal shifts in dendritic spike firing provide a novel means for backpropagating spikes to influence the final output of a cell.
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Alberta, Canada.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Fernandez
authors.forename: W Hamish
authors.initials: WH
authors.lastname: Mehaffey
authors.forename: Ray W
authors.initials: RW
authors.lastname: Turner
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004555:Electric Fish; D004557:Electric Organ / Q000166:cytology; D004558:Electric Stimulation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000166:cytology* / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin