Cellular mechanisms behind stimulus evoked quenching of variability

A wealth of experimental studies show that the trial-to-trial variability of neuronal activity is quenched during stimulus evoked responses. This fact has helped ground a popular view that the variability of spiking activity can be decomposed into two components. The first is due to irregular spike timing conditioned on the firing rate of a neuron (i.e. a Poisson process), and the second is the trial-to-trial variability of the firing rate itself. Quenching of the variability of the overall response is assumed to be a reflection of a suppression of firing rate variability. Network models have explained this phenomenon through a variety of circuit mechanisms. However, in all cases, from the vantage of a neuron embedded within the network, quenching of its response variability is inherited from its synaptic input. We analyze in vivo whole cell recordings from principal cells in layer (L) 2/3 of mouse visual cortex. While the variability of the membrane potential is quenched upon stimulation, the variability of excitatory and inhibitory currents afferent to the neuron are amplified. This discord complicates the simple inheritance assumption that underpins network models of neuronal variability. We propose and validate an alternative (yet not mutually exclusive) mechanism for the quenching of neuronal variability. We show how an increase in synaptic conductance in the evoked state shunts the transfer of current to the membrane potential, formally decoupling changes in their trial-to-trial variability. The ubiquity of conductance based neuronal transfer combined with the simplicity of our model, provides an appealing framework. In particular, it shows how the dependence of cellular properties upon neuronal state is a critical, yet often ignored, factor. Further, our mechanism does not require a decomposition of variability into spiking and firing rate components, thereby challenging a long held view of neuronal activity.