Figures 3A and 3B display dot raster plots of responses of two VCN neurons with different CFs. The variability, or jitter, in firing times of action potentials is more noticeable in the neuron with higher CF (700 Hz, Fig. 3B) than in the neuron with CF = 350 Hz (Fig. 3A). This variability is also evident in the r and CV values measured from their respective responses (Figs. 3C and 3D). Entrainment to the stimulating waveform is higher in the low-CF neuron (0.9) than in the high-CF one (0.03). Receptive field plots are shown in Figs. 3E and 3F. In both neurons, maximum firing rates are being evoked by off-CF frequencies. In the case of the neuron whose CF = 350 Hz, the frequency that elicited the maximum rate was 550 Hz, i.e., 0.65 octave above CF (Fig. 3E). In the case of the neuron with the highest CF, the maximum firing rate was produced by a 400 Hz tone (Fig. 3F), i.e., almost one octave below CF. Such shifts (Dfmax) are expressed in octaves and can be positive (e.g., Fig. 3E) or negative (e.g., Fig. 3F). Maximum firing rates computed from receptive fields in Figs. 3E and 3F are much larger than maximum rates evoked by CF tones. Those changes, DRmax, are expressed as a percentage relative to maximum CF rate. Qualitatively similar changes in Dfmax and DRmax have been shown in similar plots obtained from responses of chinchilla ANFs (Figs. 2,4 and 6 in [9]). The extent of those changes, however, is much larger in high-sync neurons than in ANFs. Insets in Figs. 3E and 3F display dot raster plots of the responses of the neurons to 550 and 400 Hz tones, respectively, at several levels (5 repetitions per stimulus level). Each neuron has a tendency to fire around 4 spikes in a 10-ms interval (especially in the inset in Fig. 3E). This entrainment is responsible for the large firing rates at 550 Hz, which produce large asymmetries in the receptive field map. Figure 4 illustrates the responses of two high-sync neurons recorded in the cat VCN. Response characteristics are similar to those in Fig. 3, with the exception of the higher values for r obtained in cat VCN neurons (compare Fig. 3D to Fig. 4D). Entrainment indices obtained from responses in Figs. 4A and 4B were 0.98 and 0.148, respectively. PSTHs in some insets in Figs. 3 and 4 were obtained from responses to CF tones and resemble histograms of ‘‘locker’’ neurons [6,11]. With the exception of the PSTH in Fig. 3A, all other histograms display instantaneous firing rates of up to 4000 spikes/sec, near the stimulus onset. Such rates indicate the ability of the respective neurons to fire one spike at the onset of each stimulus presentation with little variability in time of occurrence. (PSTHs were constructed using a binwidth = 0.25 ms.) Figure 4E also shows a decrease in the firing rate of the neuron below the spontaneous rate for a range of stimulus frequencies above CF (1000–1500 Hz). Single-tone inhibition has been previously found by Rhode [24] in VCN neuron responses and is not a property of ANFs. Dot raster plots in the insets in Figs. 4E and 4F display responses to tones whose frequencies are above CF (700 Hz) and below CF (500 Hz), respectively. Red dashed lines in Figs. 3 and 4 represent onset (i.e., 0–20 ms) firing rates evoked by 90 dB SPL tones (70 dB SPL in Fig. 4F). Again, onset firing rates evoked by above-CF tones are usually larger than those computed during a 0–50 ms window, especially in cat VCN units. Results from Figs. 2–4 suggest that asymmetries in the receptive fields of certain VCN neurons arise from entrainment and from inhibitory properties of those neurons. Figure 5 displays response area curves and PSTHs computed from responses to tones in four chinchilla high-CF VCN neurons (one neuron per row). Results in the second row (panels D, E and F) originate from axonal recordings in the VAS. The shapes of the rate profiles (left column) are asymmetric—a consequence of the Information Transmission in the Auditory Brainstem elevated firing rates evoked by low-frequency tones. Plots of vector strength as a function of stimulus frequency are in the center column. r values evoked by many below-CF tones are above 0.9, which are consistent with previous results [28]. PSTHs were classified as either PL (Fig. 5F), PLN (Fig. 5I) or OnL (Figs. 5C and 5L). Standard deviations of first-spike latencies, sFSL, computed from responses to CF tones are in the rightmost column and are all ,1 ms. Firing rates-vs.-level curves (also known as rate-intensity functions, RIFs) obtained from responses to CF tones are shown in the insets in Fig. 5. Except for the RIF in the inset in Fig. 5C, all the RIFs exhibit various degree of nonmonotonic behavior. Approximately 30% of chinchilla VCN neurons in this study were classified as nonmonotonic, using the criterion defined in [16]. None of the cat high-sync neurons in this study were classified as nonmonotonic. Response properties of highly synchronized neurons: Population study Receptive fields of high-sync neurons display changes in their shape as the stimulus level increases (Figs. 2–5). Maximum firing rates evoked by tones whose frequencies are either above or below CF can be larger than the rates evoked by CF tones. This introduces an asymmetry, or change in the ‘‘center of gravity,’’ in the response area that was previously characterized using the metrics Dfmax and DRmax (Figs. 2 and 3). Figure 6A displays Dfmax values as a function of CF for the sample of chinchilla VCN neurons collected for this report. Dfmax is positive for neurons with CF,<500 Hz and becomes negative for CF.500 Hz. The change in value for Dfmax as a function of CF is gradual and near linear (in a semi-logarithmic scale), as indicated by the line fitted to the data (continuous line in Fig. 6A). The bold dashed line in Fig. 6A corresponds to the fit performed on similar ANF data [9]. Larger amounts of frequency shifts of firing rate-vs.-frequency curves are observed in VCN neurons. The flip in polarity in those fits occurs at higher CFs for ANFs (<900 Hz). Dfmax-vs.-CF plots in Fig. 6B display a similar behavior for cat VCN neurons, except that Dfmax appears less negative than the data shown in Fig. 6A, especially for frequencies above 700 Hz. That means the shift in the center of gravity of the rate-vs.-frequency curves is smaller in cats than in chinchillas, at least for such CFs. Changes in maximum firing rate relative to maximum rate at CF, DRmax, for VCN neurons in chinchilla and cat are shown in Figs. 6C and 6D, respectively. The U-shaped pattern evident in the data in Figs. 6C and 6D indicate that asymmetries in receptive fields are more common at the lowest and highest (for the range of frequencies considered here) frequencies. Analysis of data in Figs. 6A and 6B, however, did not show statistically significant differences. Similar results were obtained from the analysis of data in Figs. 6C and 6D. Scatter plots of standard deviations of first-spike latency (FSL) against CF for high-sync neurons and ANFs in cats are displayed in Fig. 6E. Low- and mid-spontaneous ANFs have the lowest standard deviations among ANFs (red circles in Fig. 6E). High- sync neurons, however, exhibit on average the lowest value in the variability of the FSL, as shown in Fig. 6E. Statistical analysis indicates significant differences significant (p,0.01, two-sample Kolmogorov-Smirnov test) in their values for the two data populations in Fig. 6E. Vector strength values computed from responses to CF tones are shown for a population of chinchilla and cat VCN neurons (Group 1: high-sync neurons) using filled triangles in Figs. 7A and 7C, respectively. Tone levels were usually 60-dB SPL. The CF range (up to <550 Hz) for chinchilla high-sync neurons is narrower than the range in cat VCN neurons, which includes PLOS ONE | www.plosone.org 6 September 2012 | Volume 7 | Issue 9 | e44286