Stimulus selectivity is enhanced by voltage-dependent conductances in combination-sensitive neurons

Central sensory neurons often respond selectively to particular combinations of stimulus attributes, but we know little about the underlying cellular mechanisms. The weakly electric fish Gymnarchus discriminates the sign of the frequency difference (Df) between a neighbor's electric organ discharge (EOD) and its own EOD by comparing temporal patterns of amplitude modulation (AM) and phase modulation (PM). Sign-selective neurons in the midbrain respond preferentially to either positive frequency differences (Df >0 selective) or negative frequency differences (Df <0 selective). To study the mechanisms of combination sensitivity, we made whole cell intracellular recordings from sign-selective midbrain neurons in vivo and recorded postsynaptic potential (PSP) responses to AM, PM, Df >0, and Df <0. Responses to AM and PM consisted of alternating excitatory and inhibitory PSPs. These alternating responses were in phase for the preferred sign of Df and offset for the nonpreferred sign of Df. Therefore a certain degree of sign selectivity was predicted by a linear sum of the responses to AM and PM. Responses to the nonpreferred sign of Df, but not the preferred sign of Df, were substantially weaker than linear predictions, causing a significant increase in the actual degree of sign selectivity. By using various levels of current clamp and comparing our results to simple models of synaptic integration, we demonstrate that this decreased response to the nonpreferred sign of Df is caused by a reduction in voltage-dependent excitatory conductances. This finding reveals that nonlinear decoders, in the form of voltage-dependent conductances, can enhance the selectivity of single neurons for particular combinations of stimulus attributes.