In vivo Conditions Induce Faithful Encoding of Stimuli by Reducing Nonlinear Synchronization in Vestibular Sensory Neurons

Abstract

Previous studies have shown that neurons within the vestibular nuclei (VN) can faithfully encode the time course of sensory input through changes in firing rate in vivo. However, studies performed in vitro have shown that these same VN neurons often display nonlinear synchronization (i.e. phase locking) in their spiking activity to the local maxima of sensory input, thereby severely limiting their capacity for faithful encoding of said input through changes in firing rate. We investigated this apparent discrepancy by studying the effects of in vivo conditions on VN neuron activity in vitro using a simple, physiologically based, model of cellular dynamics. We found that membrane potential oscillations were evoked both in response to step and zap current injection for a wide range of channel conductance values. These oscillations gave rise to a resonance in the spiking activity that causes synchronization to sinusoidal current injection at frequencies below 25 Hz. We hypothesized that the apparent discrepancy between VN response dynamics measured in in vitro conditions (i.e., consistent with our modeling results) and the dynamics measured in vivo conditions could be explained by an increase in trial-to-trial variability under in vivo vs. in vitro conditions. Accordingly, we mimicked more physiologically realistic conditions in our model by introducing a noise current to match the levels of resting discharge variability seen in vivo as quantified by the coefficient of variation (CV). While low noise intensities corresponding to CV values in the range 0.04–0.24 only eliminated synchronization for low (<8 Hz) frequency stimulation but not high (>12 Hz) frequency stimulation, higher noise intensities corresponding to CV values in the range 0.5–0.7 almost completely eliminated synchronization for all frequencies. Our results thus predict that, under natural (i.e. in vivo) conditions, the vestibular system uses increased variability to promote fidelity of encoding by single neurons. This prediction can be tested experimentally in vitro.

Parallel Coding of First- and Second-Order Stimulus Attributes by Midbrain Electrosensory Neurons

“…As such, neurons that reliably display nonlinear rectification (i.e., are driven into cessation of firing) at some stimulus phases must then reliably fire action potentials at other stimulus phases and thus also display phase locking (Savard et al, 2011). Phase locking is thus a nonlinear phenomenon that gives rise to peaks in the spike train power spectrum at integer multiples (i.e., higher harmonics) of the frequencies contained in the stimulus waveform (i.e., the fundamental frequencies) (Ewert et al, 2008;Savard et al, 2011;Schneider et al, 2011). We therefore quantified phase locking by computing the ratio of the power at the second harmonic (i.e., 3 times the fundamental frequencies) to that at the fundamental frequencies as done previously (Schneider et al, 2011).…”

“…Phase locking is thus a nonlinear phenomenon that gives rise to peaks in the spike train power spectrum at integer multiples (i.e., higher harmonics) of the frequencies contained in the stimulus waveform (i.e., the fundamental frequencies) (Ewert et al, 2008;Savard et al, 2011;Schneider et al, 2011). We therefore quantified phase locking by computing the ratio of the power at the second harmonic (i.e., 3 times the fundamental frequencies) to that at the fundamental frequencies as done previously (Schneider et al, 2011). Specifically, for 40 -60 Hz noise stimulation, we obtained a phase locking index by dividing the value of the spike train power spectrum at 150 Hz by its value at 50 Hz.…”

“…We note that other measures that can be used to quantify phase locking such as vector strength (Mardia and Jupp, 1999) can be nonzero even when the relationship between the stimulus waveform and the neuronal output firing rate is linear in nature (Schneider et al, 2011), a situation that does not give rise either to phase locking as defined above or nonlinear rectification, and are thus not appropriate in this case.…”

“…4C). Such rectification is accompanied by phase locking since the onset of action potential firing must then occur reliably at other portions of the stimulus (Savard et al, 2011;Schneider et al, 2011). In contrast, ELL neurons with higher firing rates tended to fire action potentials throughout the stimulus and, as such, tended to display less phase locking (Fig.…”

The vestibular system: multimodal integration and encoding of self-motion for motor control

“…The higher variability displayed by vestibular central neurons could potentially serve to prevent phase locking or entrainment [38–39]. For example, in the visual system thalamic relay cells transmit detailed information in their spike trains [14–15], while cortical neurons display large variability in their responses [40].…”