%0 Journal Article %A Yann Zerlaut %A Alain Destexhe %T Heterogeneous Firing Responses Predict Diverse Couplings to Presynaptic Activity in mice Layer V Pyramidal Neurons %D 2016 %R 10.1101/091587 %J bioRxiv %P 091587 %X In the present study, we present a theoretical framework combining experimental characterizations and analytical calculus to capture the firing rate input-output properties of single neurons in the fluctuation-driven regime. We use this framework to investigate the functional impact of the heterogeneity in firing responses found experimentally in young mice layer V pyramidal cells. We first design and calibrate in vitro a simplified morphological model of layer V pyramidal neurons with a dendritic tree following Rall’s branching rule. Then, we propose an analytical derivation for the membrane potential fluctuations at the soma as a function of the properties of the synaptic bombardment in dendrites. This mathematical description allows us to easily emulate various forms of presynaptic activities: either balanced, unbalanced, synchronized, purely proximal or purely distal synaptic activity. We found that those different forms of activity led to various comodulations of the membrane potential fluctuation properties, thus raising the question whether individual neurons might differentially couple to specific forms of activity because of their different firing responses. We indeed found such a heterogeneous response for all types of presynaptic activity. This heterogeneity was explained by different levels of cellular excitability in the case of the balanced, unbalanced, synchronized and purely distal activity. A notable exception appeared for proximal activity: increasing activity could either promote firing response in some cells or suppress it in some other cells whatever their individual excitability. This behavior could only be explained by various sensitivities to the speed of the fluctuations, which was previously associated to heterogeneous levels of sodium channel inactivation and density. Because local network connectivity targets rather proximal region, our results suggest that this biophysical heterogeneity might be relevant to neocortical processing by controlling how individual neurons couple to local network activity.Author summary Neocortical processing of sensory input relies on the specific activation of subpopulations within the cortical network. Though specific circuitry is thought to be the primary mechanism underlying this functional principle, we explore here a putative complementary mechanism: whether diverse biophysical features in single neurons contribute to such differential activation. in a previous study, we reported that, in young mice visual cortex, individual neurons differ not only in their excitability but also in their sensitivities to the properties of the membrane potential fluctuations. In the present work, we analyze how this heterogeneity is translated into diverse input-output properties in the context of low synchrony population dynamics. As expected, we found that individual neurons couple differentially to specific form of presynaptic activity (emulating afferent stimuli of various properties) mostly because of their differences in excitability. However, we also found that the response to proximal activity was controlled by the sensitivity to the speed of the fluctuations (which can be linked to various levels of density of sodium channels and sodium inactivation). Our study thus proposes a novel functional impact of biophysical heterogeneity: because of their various firing responses, individual neurons will differentially couple to local network activity. %U https://www.biorxiv.org/content/biorxiv/early/2016/12/04/091587.full.pdf