Heterogeneous firing rate response of mouse layer V pyramidal neurons in the fluctuation-driven regime

Key points: We recreated in vitro the fluctuation-driven regime observed at the soma during asynchronous network activity in vivo and we studied the firing rate response as a function of the properties of the membrane potential fluctuations. We provide a simple analytical template that captures the firing response of both pyramidal neurons and various theoretical models. We found a strong heterogeneity in the firing rate response of layer V pyramidal neurons: in particular, individual neurons differ not only in their mean excitability level, but also in their sensitivity to fluctuations. Theoretical modelling suggest that this observed heterogeneity might arise from various expression levels of the following biophysical properties: sodium inactivation, density of sodium channels and spike frequency adaptation.

Abstract: Characterizing the input-output properties of neocortical neurons is of crucial importance for understanding the properties emerging at the network level. In the regime of low-rate irregular firing (such as in the awake state), determining those properties for neocortical cells remains, however, both experimentally and theoretically challenging. Here, we studied this problem using a combination of theoretical modelling and in vitro experiments. We first identified, theoretically, three somatic variables that describe the dynamical state at the soma in this fluctuation-driven regime: the mean, standard deviation and time constant of the membrane potential fluctuations. Next, we characterized the firing rate response of individual layer V pyramidal cells in this three-dimensional space by means of perforated-patch recordings and dynamic clamp in the visual cortex of juvenile mice in vitro. We found that individual neurons strongly differ not only in terms of their excitability, but also, and unexpectedly, in their sensitivities to fluctuations. Finally, using theoretical modelling, we attempted to reproduce these results. The model predicts that heterogeneous levels of biophysical properties such as sodium inactivation, sharpness of sodium activation and spike frequency adaptation account for the observed diversity of firing rate responses. Because the firing rate response will determine population rate dynamics during asynchronous neocortical activity, our results show that cortical populations are functionally strongly inhomogeneous in young mouse visual cortex, which should have important consequences on the strategies of cortical computation at early stages of sensory processing.