When Less Is More: Non-monotonic Spike Sequence Processing in Neurons

Fundamental response properties of neurons centrally underly the computational capabilities of both individual nerve cells and neural networks. Most studies on neuronal input-output relations have focused on continuous-time inputs such as constant or noisy sinusoidal currents. Yet, most neurons communicate via exchanging action potentials (spikes) at discrete times. Here, we systematically analyze the stationary spiking response to regular spiking inputs and reveal that it is generically non-monotonic. Our theoretical analysis shows that the underlying mechanism relies solely on a combination of the discrete nature of the communication by spikes, the capability of locking output to input spikes and limited resources required for spike processing. Numerical simulations of mathematically idealized and biophysically detailed models, as well as neurophysiological experiments confirm and illustrate our theoretical predictions.Author Summary: Brain function relies on robust communication between a huge number of nerve cells (neurons) that exchange short-lasting electrical pulses (called action potentials or spikes) at certain times. How nerve cells process their spiking inputs to generate spiking outputs thus is key not only to individual neurons’ computational capabilities but also to the collective dynamics of neuronal networks. Here we analyze the response properties of neurons to regular spike sequence inputs. We find that neurons typically respond in a non-monotonic way. Output frequency mostly increases with input frequency as expected but sometimes output frequency necessarily decreases upon increasing the input frequency. Our theoretical analysis predicts that spiking neurons commonly exhibit such non-monotonic response properties. Simulations of simple mathematical and complex computational models as well as neurophysiological experiments confirm our theoretical predictions.