TY - JOUR T1 - Neuromodulation Reduces Interindividual Variability of Neuronal Output JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0166-22.2022 VL - 9 IS - 4 SP - ENEURO.0166-22.2022 AU - Anna C. Schneider AU - Omar Itani AU - Dirk Bucher AU - Farzan Nadim Y1 - 2022/07/01 UR - http://www.eneuro.org/content/9/4/ENEURO.0166-22.2022.abstract N2 - In similar states, neural circuits produce similar outputs across individuals despite substantial interindividual variability in neuronal ionic conductances and synapses. Circuit states are largely shaped by neuromodulators that tune ionic conductances. It is therefore possible that, in addition to producing flexible circuit output, neuromodulators also contribute to output similarity despite varying ion channel expression. We studied whether neuromodulation at saturating concentrations can increase the output similarity of a single identified neuron across individual animals. Using the lateral pyloric (LP) neuron of the crab stomatogastric ganglion, we compared the variability of f–I (frequency–current) curves and rebound properties in the presence of neuropeptides. The two neuropeptides we used converge to activate the same target current, which increases neuronal excitability. Output variability was lower in the presence of the neuropeptides, regardless of whether the neuropeptides significantly changed the mean of the corresponding parameter or not. However, the addition of the second neuropeptide did not add further to the reduction of variability. With a family of computational LP-like models, we explored how increased excitability and target variability contribute to output similarity and found two mechanisms: saturation of the responses and a differential increase in baseline activity. Saturation alone can reduce the interindividual variability only if the population shares a similar ceiling for the responses. In contrast, the reduction of variability due to the increase in baseline activity is independent of ceiling effects. ER -