The domain of neuronal firing on a plane of input current and conductance

The activation of neurotransmitter receptors increases the current flow and membrane conductance and thus controls the firing rate of a neuron. In the present work, we justified the two-dimensional representation of a neuronal input by voltage-independent current and conductance and obtained experimentally and numerically a complete input-output (I/O) function. The dependence of the steady-state firing rate on the input current and conductance was studied as a two-parameter I/O function. We employed the dynamic patch clamp technique in slices to get this dependence for the whole domain of two input signals that evoke stationary spike trains in a single neuron (Ω-domain). As found, the Ω-domain is finite and an additional conductance decreases the range of spike-evoking currents. The I/O function has been reproduced in a Hodgkin-Huxley-like model. Among the simulated effects of different factors on the I/O function, including passive and active membrane properties, external conditions and input signal properties, the most interesting were: the shift of the right boundary of the Ω-domain (corresponding to the exCitation block) leftwards due to the decrease of the maximal potassium conductance; and the reduction of the Ω-domain by the decrease of the maximal sodium concentration. As found in experiments and simulations, the Ω-domain is reduced by the decrease of extracellular sodium concentration, by cooling, and by adding slow potassium currents providing interspike interval adaptation; the Ω-domain height is increased by adding color noise. Our modeling data provided a generalization of I/O dependencies that is consistent with previous studies and our experiments. Our results suggest that both current flow and membrane conductance should be taken into account when determining neuronal firing activity.