Amplitude modulation coding in awake mice and squirrel monkeys

Abstract

Both mice and primates are used to model the human auditory system. The primate order possesses unique cortical specializations that govern auditory processing. Given the power of molecular and genetic tools available in the mouse model, it is essential to understand the similarities and differences in auditory cortical processing between mice and primates. To address this issue, we directly compared temporal encoding properties of neurons in the auditory cortex of awake mice and awake squirrel monkeys (SQMs). Stimuli were drawn from a sinusoidal amplitude modulation (SAM) paradigm, which has been used previously both to characterize temporal precision and to model the envelopes of natural sounds. Neural responses were analyzed with linear template-based decoders. In both species, spike timing information supported better modulation frequency discrimination than rate information, and multiunit responses generally supported more accurate discrimination than single-unit responses from the same site. However, cortical responses in SQMs supported better discrimination overall, reflecting superior temporal precision and greater rate modulation relative to the spontaneous baseline and suggesting that spiking activity in mouse cortex was less strictly regimented by incoming acoustic information. The quantitative differences we observed between SQM and mouse cortex support the idea that SQMs offer advantages for modeling precise responses to fast envelope dynamics relevant to human auditory processing. Nevertheless, our results indicate that cortical temporal processing is qualitatively similar in mice and SQMs and thus recommend the mouse model for mechanistic questions, such as development and circuit function, where its substantial methodological advantages can be exploited. NEW & NOTEWORTHY To understand the advantages of different model organisms, it is necessary to directly compare sensory responses across species. Contrasting temporal processing in auditory cortex of awake squirrel monkeys and mice, with parametrically matched amplitude-modulated tone stimuli, reveals a similar role of timing information in stimulus encoding. However, disparities in response precision and strength suggest that anatomical and biophysical differences between squirrel monkeys and mice produce quantitative but not qualitative differences in processing strategy.

Keywords: amplitude modulation; auditory cortex; species comparison; temporal processing.

Fig. 1.

Simple linear decoders were used to determine how effectively the modulation frequency of sinusoidal amplitude modulation (SAM) can be discriminated on the basis of cortical spiking patterns represented at different temporal resolutions. A: gray curves illustrate the amplitude envelopes for SAM at 4, 8, 16, 32, 64, and 128 Hz. B: event raster of a single unit’s responses to SAM tones recorded from the auditory cortex of a mouse. A single trial to be decoded is highlighted in magenta (see methods). The best frequency of this site was 24.25 kHz; the carrier frequency of the SAM tones was 10 kHz. C: rate-only decoder: the spike count from a single trial (magenta) is compared with the trial-averaged counts across all trials of each stimulus (cyan). The trial to be decoded is excluded from the templates. The template that best matches the trial is indicated with an asterisk. D and E: timing-only decoder: the spikes from a single trial (magenta bars and dots at top) are binned and compared with rate-normalized trial-averaged binned responses at 2 time resolutions: 10 ms (D) and 50 ms (E). The trial to be decoded is excluded from the templates. The template that best matches the trial is indicated with an asterisk. Single-trial PSTHs are scaled for graphical convenience. F and G: combined decoder: the spikes from a single trial (magenta bars and dots at top) are binned and compared with unnormalized trial-averaged binned responses for 10-ms bins (F) and 50-ms bins (G). The trial to be decoded is excluded from the templates. The template that best matches the trial is indicated with an asterisk. Single-trial PSTHs are scaled for graphical convenience. H: decoding accuracy is defined as the number of trials matched correctly divided by the total number of trials; accuracies are plotted by time resolution below each decoder. Optimal bin size is defined as the bin size at which decoding accuracy is highest (magenta circles).

Fig. 2.

Modulation frequency was more accurately decoded from squirrel monkey (SQM) than mouse cortical responses at fine temporal resolutions, although timing information contributes more to decoding than rate; multiunit (MU) responses tend to decode more accurately than single-unit (SU) responses in both organisms. A and D, a: decoding accuracy is plotted by bin size for SQM and mouse SUs (A) and MUs (D). Points that do not exceed the threshold for significance (see methods) are shown in gray. b: Mean (solid line) decoding accuracies ± 2 SE (shaded area) are plotted by bin size for SQM and mouse SUs and MUs. c: % of SUs and MUs with accuracies exceeding the threshold for significance are plotted by bin size for SQM and mouse. B and E, a and b: timing-only decoder accuracy is plotted against rate-only accuracy for SQM and mouse SUs (B) and MUs (E) for bin sizes of 5 ms (a) and 25 ms (b). Gray lines indicate significance thresholds. c: Box and whisker plots show differences between timing-only and rate-only accuracy for SUs and MUs for both SQM and mouse. C and F, a: histograms show the distributions of optimal bin sizes for SQM and mouse SUs (SQM: n = 271; mouse: n = 19) and MUs (SQM: n = 191; mouse: n = 155) that produced accuracies exceeding the threshold for significance (for at least 1 bin size). b: Accuracy at optimal bin size is plotted by bin size for SQM and mouse SUs and MUs. Only significant values are shown. c: Histograms show the distributions of accuracies for significantly decoding SQM and mouse units. Desaturated bars at bottom show % of all units that are insignificant (n.s.) at all bin sizes. G, a: rate-only decoding accuracy for each MU is plotted against rate-only decoding accuracy for each SU isolated on that recording channel for SQMs and mice. b: Timing-only decoding accuracy for each MU is plotted analogously (as in a) against SU timing-only decoding accuracy. c: Combined decoding accuracy for each MU is plotted against combined decoding accuracy for each SU. d: Boxplots illustrate differences (Δ) between MU and SU decoding accuracies for the decoders for SQMs and mice. *P < 0.05, **P < 0.005, ***P < 0.0005.

Fig. 3.

SAM responses from squirrel monkeys (SQMs) are more precisely entrained and more reliable at higher modulation frequencies than responses from mice. A–D, a: event raster from a representative SQM single unit (SU; A), SQM multiunit (MU) from the same channel (C), mouse SU (B), and mouse MU from the same channel (D). Trials in color are included in the binned counts shown in color in c; trials in black are included in the binned counts shown in black. In A and B, insets show the mean ± SE waveform of the unit. b: Phase histograms are generated by folding response PSTHs on the modulation period of the sound. c: PSTHs generated with 8 randomly selected trials (color) are correlated with PSTHs generated using the other 7 trials (black). d, Top: vector strength (VS) is plotted as a function of modulation frequency. Filled circles indicate significant VS (Rayleigh statistic > 13.816, corresponds to P < 0.001). Bottom: trial similarity (TS), the mean correlation between PSTHs, is plotted as a function of modulation frequency. Filled circles indicated significant TS (P < 0.05, Monte Carlo simulated null distribution). E and F, a: % of SUs (E) and MUs (F) recorded from SQMs and mice that have significant VS at each modulation frequency. b: Significant VS values for each SU (E) and MU (F) for SQMs and mice at each modulation frequency. G and H, a: % of SUs (G) and MUs (H) recorded from SQMs and mice that have significant TS at each modulation frequency. b: Significant TS values for each SU (G) and MU (H) for SQMs and mice at each modulation frequency.

Fig. 4.

Evoked firing rate is more modulated above baseline in squirrel monkey (SQM) than mouse single units (SUs) and multiunits (MUs), and cells with large rate modulations are coextensive with high decoding accuracy; the range of evoked firing rates is predictive of decoding accuracy in both organisms. A and B, a: event raster from a representative mouse SU (A) and mouse MU from the same channel (B). b: Mean ± SE evoked firing rate (FR) as a function of modulation frequency (dark solid/shaded lines), spontaneous firing rate (dashed lines) calculated from the 100 ms before sound onset, and mean evoked firing rate across frequency (bright solid lines). RMI, rate modulation index. C and D, a: marginal histograms show the distributions of spontaneous firing rates for SQM and mouse SUs (E) and MUs (F). b: Average evoked firing rate vs. spontaneous firing rate for SQM and mouse SUs and MUs. c: Vertical marginal histograms show the distributions of average evoked firing rates. E and F, a: marginal histograms show the distributions of RMI for SQM and mouse SUs and MUs. An RMI of 0 indicates no difference between evoked and spontaneous activity; an RMI of 1 indicates evoked activity but no spontaneous activity; an RMI of −1 indicates a cell that completely suppresses spontaneous activity in response to sound. b: Combined decoding accuracy at optimal bin size is plotted against RMI for SQM and mouse SUs and MUs. Vertical dashed lines at 0.3 and −0.3 indicate RMI values corresponding to a 2-fold increase in mean evoked firing rate relative to baseline. c: Vertical marginal histograms show the distributions of decoding accuracies for SQM and mouse MUs and SUs. G and H, a: marginal histograms show the distributions of rate spans (the difference between the max and min evoked firing rates) for SQM and mouse SUs and MUs. b: Rate span is plotted against combined decoding accuracy at optimal bin size for SQM and mouse SUs and MUs. c: Vertical marginal histograms show the distributions of decoding accuracies for SQM and mouse MUs and SUs.