Dynamic interaction of I_h and I_K-LVA during trains of synaptic potentials in principal neurons of the medial superior olive

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-clamprecordings fromMSO principal neuronsingerbil brainstem slices,weexamined interactions between two major currents controlling subthreshold synaptic integration: a low-voltage-activated potassium current (I_K-LVA) and ahyperpolarization-activated cation current (I_h). Both I_h and I_K-LVA contributed stronglyto 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 peaksof EPSPs increasedby only afew millivolts during trains. Using a model of an MSO cell, we demonstrated that the nearly uniform response during modest depolarizing stimuli relied on changes inI_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 betweenI_h andI_K-LVA helpstomaintainanearlyuniform shapeofindividualsynaptic responses, andweshow thatthetime resolutionofsynaptic coincidence detection canbemaintainedduring trainsifEPSC sizegraduallydecreases (asinsynaptic depression), counteracting slow increases in excitability.