Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons

The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter—describing somatic integration—and the spike-history filter—accounting for spike-frequency adaptation—dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations.Author Summary: Over the last decades, a variety of simplified spiking models have been shown to achieve a surprisingly high performance in predicting the neuronal responses to in vitro somatic current injections. Because of the complex adaptive behavior featured by cortical neurons, this success is however restricted to limited stimulus ranges: model parameters optimized for a specific input regime are often inappropriate to describe the response to input currents with different statistical properties. In the present study, a new spiking neuron model is introduced that captures single-neuron computation over a wide range of input statistics and explains different aspects of the neuronal dynamics within a single framework. Our results indicate that complex forms of single neuron adaptation are mediated by the nonlinear dynamics of the firing threshold and that the input-output transformation performed by cortical pyramidal neurons can be intuitively understood in terms of an enhanced Generalized Linear Model in which both the input filter and the spike-history filter adapt to the input statistics.