Ionic and morphological contributions to the variable gain of membrane responses in layer 2/3 pyramidal neurons of mouse primary visual cortex

Many neuronal cell types exhibit a sliding scale of neuronal excitability in the subthreshold voltage range. This is due to a variable contribution of different voltage-gated ion channels, leading to scaling of input resistance (RN) as a function of membrane potential (Vm) and a voltage-dependent dynamic gain of neuronal responsiveness. In layer 2/3 pyramidal neurons within the primary visual cortex (V1), this response influences sensory processing by tightening neuronal tuning to preferred orientations, but the identity of the ionic conductances involved remains unknown. Here, we used in vitro physiological recordings in acute slices to identify the contributions of several voltage-dependent conductances to the dynamic gain of membrane responses in layer 2/ 3 pyramidal neurons in mouse primary visual cortex. We found that the steep voltage dependence of input resistance in these cells was mediated in part by a combination of persistent sodium, inwardly rectifying potassium, and hyperpolarization-activated nonselective cation channels. In addition, the steepness of the slope of the RN/Vm relationship was inversely correlated with the number of branches on the proximal apical dendrite. These data have uncovered physiological and morphological factors that underlie the scaling of membrane responses in L2/3 neurons of rodent V1. Regulation of these channels would serve as a mechanism of real-time neuromodulation of neuronal processing of sensory information. NEW & NOTEWORTHY Layer 2/3 pyramidal neurons in primary visual cortex scale subthreshold voltage responses with resting membrane potential because RN increases as Vm is depolarized. Here, we uncovered the voltage-dependent contributions of NaP, Kir, and HCN conductances toward this behavior, and we additionally demonstrated that the strength of the RN/Vm relationship is inversely correlated with proximal branching along the apical dendrite.