Channel expression aligns with dendritic conductance load in the reinforcing, not compensatory, direction in cortical GABAergic neurons

Abstract

Neurons could offset the conductance load imposed by their dendrites through channel expression (compensation), or channel expression could move with that load (reinforcement); which arrangement holds in adult cortex is unknown. Writing rheobase as the product of input conductance and an effective-voltage factor turns the question into a sign test. In mouse cortical GABAergic Patch-seq neurons, after removal of transcriptomic type and covariates, an out-of-fold channel-gene score co-varies positively with residual input conductance (median Spearman {rho} = 0.32 over 20 cross-fitting splits, n = 493) and with a conductance score predicted from dendritic morphology alone ({rho} = 0.23, n = 483). The association is carried mainly by Sst and Pvalb cells and is close to zero in Vip cells. Its slope on the compensation axis is 0.13, against -1 for compensation and 0 for independence, so the finding concerns direction rather than magnitude: it excludes a population-wide compensation rule without implying strong amplification. Reduced NEURON models show that a compensatory correction is biophysically feasible, and the morphology-derived conductance predictor transfers from mouse to human reconstructions ({rho} = 0.27, n = 128).