Neural heterogeneities determine response characteristics to second-, but not first-order stimulus features

Neural heterogeneities are seen ubiquitously, but how they determine neural response properties remains unclear. Here we show that heterogeneities can either strongly, or not at all, influence neural responses to a given stimulus feature. Specifically, we recorded from peripheral electroreceptor neurons, which display strong heterogeneities in their resting discharge activity, in response to naturalistic stimuli consisting of a fast time-varying waveform (i.e., first-order) whose amplitude (i.e., second-order or envelope) varied slowly in the weakly electric fish Apteronotus leptorhynchus. Although electroreceptors displayed relatively homogeneous responses to first-order stimulus features, further analysis revealed two subpopulations with similar sensitivities that were excited or inhibited by increases in the envelope, respectively, for stimuli whose frequency content spanned the natural range. We further found that a linear-nonlinear cascade model incorporating the known linear response characteristics to first-order features and a static nonlinearity accurately reproduced experimentally observed responses to both first- and second-order features for all stimuli tested. Importantly, this model correctly predicted that the response magnitude is independent of either the stimulus waveform's or the envelope's frequency content. Further analysis of our model led to the surprising prediction that the mean discharge activity can be used to determine whether a given neuron is excited or inhibited by increases in the envelope. This prediction was validated by our experimental data. Thus, our results provide key insight as to how neural heterogeneities can determine response characteristics to some, but not other, behaviorally relevant stimulus features.