Enhanced Activation of HCN Channels Reduces Excitability and Spike-Timing Regularity in Maturing Vestibular Afferent Neurons.

Vestibular ganglion neurons (VGNs) transmit information along parallel neuronal pathways whose signature distinction is variability in spike-timing; some fire at regular intervals while others fire at irregular intervals. The mechanisms driving timing differences are not fully understood but two opposing (but not mutually exclusive) hypotheses have emerged. In the first, regular-spiking is inversely correlated to the density of low-voltage-gated potassium currents (IKL). In the second, regular spiking is directly correlated to the density of hyperpolarization-activated cyclic nucleotide-sensitive currents (IH). Supporting the idea that variations in ion channel composition shape spike-timing, VGNs from the first postnatal week respond to synaptic-noise-like current injections with irregular-firing patterns if they have IKL and with more regular firing patterns if they do not. However, in vitro firing patterns are not as regular as those in vivo Here we considered whether highly-regular spiking requires IH currents and whether this dependence emerges later in development after channel expression matures. We recorded from rat VGN somata of either sex aged postnatal day (P)9-P21. Counter to expectation, in vitro firing patterns were less diverse, more transient-spiking, and more irregular at older ages than at younger ages. Resting potentials hyperpolarized and resting conductance increased, consistent with developmental upregulation of IKL Activation of IH (by increasing intracellular cAMP) increased spike rates but not spike-timing regularity. In a model, we found that activating IH counter-intuitively suppressed regularity by recruiting IKL Developmental upregulation in IKL appears to overwhelm IH These results counter previous hypotheses about how IH shapes vestibular afferent responses.SIGNIFICANCE STATEMENT Vestibular sensory information is conveyed on parallel neuronal pathways with irregularly-firing neurons encoding information using a temporal code and regularly-firing neurons using a rate code. This is a striking example of spike-timing statistics influencing information coding. Previous studies from immature vestibular ganglion neurons (VGNs) identified hyperpolarization-activated mixed cationic currents (IH) as driving highly-regular spiking and proposed that this influence grows with the current during maturation. We found that IH becomes less influential, likely because maturing VGNs also acquire low-voltage-gated potassium currents (IKL), whose inhibitory influence opposes IH Because efferent activity can partly close IKL, VGN firing patterns may become more receptive to extrinsic control. Spike-timing regularity likely relies on dynamic ion channel properties and complementary specializations in synaptic connectivity.

Comparing stimulus-frequency otoacoustic emissions measured by compression, suppression, and spectral smoothing.

Stimulus-frequency otoacoustic emissions (SFOAEs) have been measured in several different ways, including (1) nonlinear compression, (2) two-tone suppression, and (3) spectral smoothing. Each of the three methods exploits a different cochlear phenomenon or signal-processing technique to extract the emission. The compression method makes use of the compressive growth of emission amplitude relative to the linear growth of the stimulus. The emission is defined as the complex difference between ear-canal pressure measured at one intensity and the rescaled pressure measured at a higher intensity for which the emission is presumed negligible. The suppression method defines the SFOAE as the complex difference between the ear-canal pressure measured with and without a suppressor tone at a nearby frequency. The suppressor tone is presumed to substantially reduce or eliminate the emission. The spectral smoothing method involves convolving the complex ear-canal pressure spectrum with a smoothing function. The analysis exploits the differing latencies of stimulus and emission and is equivalent to windowing in the corresponding latency domain. Although the three methods are generally assumed to yield identical emissions, no equivalence has ever been established. This paper compares human SFOAEs measured with the three methods using procedures that control for temporal drifts, contamination of the calibration by evoked emissions, and other potential confounds. At low stimulus intensities, SFOAEs measured using all three methods are nearly identical. At higher intensities, limitations of the procedures contribute to small differences, although the general spectral shape and phase of the three SFOAEs remain similar. The near equivalence of SFOAEs measured by compression, suppression, and spectral smoothing indicates that SFOAE characteristics are not mere artifacts of measurement methodology.