title: Dynamic interaction of Ih and IK-LVA during trains of synaptic potentials in principal neurons of the medial superior olive.
abstract: In neurons of the medial superior olive (MSO), voltage-gated ion channels control the submillisecond time resolution of binaural coincidence detection, but little is known about their interplay during trains of synaptic activity that would be experienced during auditory stimuli. Here, using modeling and patch-clamp recordings from MSO principal neurons in gerbil brainstem slices, we examined interactions between two major currents controlling subthreshold synaptic integration: a low-voltage-activated potassium current (I(K-LVA)) and a hyperpolarization-activated cation current (I(h)). Both I(h) and I(K-LVA) contributed strongly to the resting membrane conductance and, during trains of simulated EPSPs, exhibited cumulative deactivation and inactivation, respectively. In current-clamp recordings, regular and irregular trains of simulated EPSCs increased input resistance up to 60%, effects that accumulated and decayed (after train) over hundreds of milliseconds. Surprisingly, the mean voltage and peaks of EPSPs increased by only a few millivolts during trains. Using a model of an MSO cell, we demonstrated that the nearly uniform response during modest depolarizing stimuli relied on changes in I(h) and I(K-LVA), such that their sum remained nearly constant over time. Experiments and modeling showed that, for simplified binaural stimuli (EPSC pairs in a noisy background), spike probability gradually increased in parallel with the increasing input resistance. Nevertheless, the interplay between I(h) and I(K-LVA) helps to maintain a nearly uniform shape of individual synaptic responses, and we show that the time resolution of synaptic coincidence detection can be maintained during trains if EPSC size gradually decreases (as in synaptic depression), counteracting slow increases in excitability.
authors.affiliation: Section of Neurobiology and Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712-0248, USA.
authors.forename: Sukant
authors.initials: S
authors.lastname: Khurana
authors.forename: Michiel W H
authors.initials: MW
authors.lastname: Remme
authors.forename: John
authors.initials: J
authors.lastname: Rinzel
authors.forename: Nace L
authors.initials: NL
authors.lastname: Golding
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002316:Cardiotonic Agents / Q000494:pharmacology; D003198:Computer Simulation; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D005849:Gerbillinae; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017711:Nonlinear Dynamics; D016011:Normal Distribution; D009847:Olivary Nucleus / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D011743:Pyrimidines; C081506:dendrotoxin K; C082246:ICI D2788