High-Frequency Resonance in the Gerbil Medial Superior Olive

Abstract

A high-frequency, subthreshold resonance in the guinea pig medial superior olive (MSO) was recently linked to the efficient extraction of spatial cues from the fine structure of acoustic stimuli. We report here that MSO neurons in gerbil also have resonant properties and, based on our whole-cell recordings and computational modeling, that a low-voltage-gated potassium current, IKLT, underlies the resonance. We show that resonance was lost following dynamic clamp replacement of IKLT with a leak conductance and in the model when voltage-gating of IKLT was suppressed. Resonance was characterized using small amplitude sinusoidal stimuli to generate impedance curves as typically done for linear systems analysis. Extending our study into the nonlinear, voltage-dependent regime, we increased stimulus amplitude and found, experimentally and in simulations, that the subthreshold resonant frequency (242Hz for weak stimuli) increased continuously to the resonant frequency for spiking (285Hz). The spike resonance of these phasic-firing (type III excitable) MSO neurons and of the model is of particular interest also because previous studies of resonance typically involved neurons/models (type II excitable, such as the standard Hodgkin-Huxley model) that can fire tonically for steady inputs. To probe more directly how these resonances relate to MSO neurons as slope-detectors, we presented periodic trains of brief, fast-rising excitatory post-synaptic potentials (EPSCs) to the model. While weak subthreshold EPSC trains were essentially low-pass filtered, resonance emerged as EPSC amplitude increased. Interestingly, for spike-evoking EPSC trains, the threshold amplitude at spike resonant frequency (317Hz) was lower than the single ESPC threshold. Our finding of a frequency-dependent threshold for repetitive brief EPSC stimuli and preferred frequency for spiking calls for further consideration of both subthreshold and suprathreshold resonance to fast and precise temporal processing in the MSO.

Resonance Properties in Auditory Brainstem Neurons

“…We therefore derived resonance frequencies for varying amplitudes I ( f ) of the ZAP stimulus (Figures 2A,B ; 14 neurons, 91 trials of P15 MSO; 12 neurons, 82 trials of >P60 MSO) and varying magnitudes I 0 of an additionally applied constant current (Figures 2C,D ; 10 neurons, 41 trials of P15 MSO; 10 neurons, 32 trials >P60 MSO). As previously described (Mikiel-Hunter et al, 2016 ), both an increase in amplitude and an increase in I 0 yielded generally larger resonance frequencies (Figures 2B,D ). The correlation between resonance frequency f r and amplitude was significant in all groups (Pearson's r = 0.71, p < 0.0001 for P15, n = 91 stimuli, r = 0.60, p < 0.0001 for P > 60, n = 82; r = 0.80, p < 0.0001 for both age groups, n = 173).…”

“…In the initial data the depolarizing resonance frequency f r appeared to scatter over a large range for individual neuron types (Figure 1E ). In previous papers (Rotstein, 2015 ; Mikiel-Hunter et al, 2016 ), it was shown that f r increases with the average membrane depolarization indicating a non-linear voltage-dependent gating of the subthreshold conductances. Thus, we expected, that our observed scatter of f r can be explained by such factors as well.…”

Extraction of Inter-Aural Time Differences Using a Spiking Neuron Network Model of the Medial Superior Olive

“…The firing rate of the MSO model is of course strongly influenced by the balance between the excitatory inputs from the ANFs and the inhibitory inputs from the GBCs but it is additionally modulated by changes of the spiking thresholds. MSO neurons have been found to exhibit subthreshold resonance (Remme et al, 2014 ; Mikiel-Hunter et al, 2016 ) which introduces frequency dependent thresholds. The MSO model used in this study exhibited a resonance frequency at about 260 Hz (see Figure S2 ) which is in agreement with the resonance frequencies found in electrophysiological studies (Remme et al, 2014 ; Mikiel-Hunter et al, 2016 ).…”

“…MSO neurons have been found to exhibit subthreshold resonance (Remme et al, 2014 ; Mikiel-Hunter et al, 2016 ) which introduces frequency dependent thresholds. The MSO model used in this study exhibited a resonance frequency at about 260 Hz (see Figure S2 ) which is in agreement with the resonance frequencies found in electrophysiological studies (Remme et al, 2014 ; Mikiel-Hunter et al, 2016 ). The reduced spiking threshold around 260 Hz in combination with the dynamics of the synaptic inputs results in a peak in MSO response seen in Figure 3F , which also corresponds to the peak in sensitivity shown in Figure 3D .…”

“…They recorded the response of neurons that phase-locked to the envelopes of amplitude-modulated tones and also showed a peak in the response at a modulation rate of 300 Hz. In the model, the responses were influenced by the subthreshold resonance of MSO neurons, which is due to the dynamics of the low threshold potassium current (Mikiel-Hunter et al, 2016 ). This resonance would also explain the results by Yin and Chan ( 1990 ).…”