Fig 5. Chloride accumulation has a progressive degenerative effect on the input-output function of neurons.

Neuronal input-output curves from instantaneous firing rate (IFR) represented as heatmaps using synapses with continuous fluctuating conductances instead of discrete inputs. Top, example traces of neuronal membrane potential showing action potential firing over 1 s (and at 10 s) from 5 repeated simulation runs (grey-bordered squares in the heatmaps). The IFR of the neuron was taken at 20 ms, 100 ms, 500 ms 1000 ms and 10000 ms using a backward integration window (Δt) of 20 ms as an average of the 5 simulation runs. Input-output curves represented as heatmaps of IFR for relative excitatory (different columns in an individual heatmap) and inhibitory (different rows in an individual heatmap) conductances. The top row of heatmaps is where simulations were conducted with dynamic Cl^-. The second row is for identical simulations with static Cl^-. The third row is the difference in IFR (ΔIFR) between the two. The bottom row is the [Cl^-]_i at the time point for that panel (a logarithmic scale was used to visualise the small changes at 20 ms). Right inset, example input-output curve for simulations with (solid trace) and without (dashed trace) dynamic Cl^-over 1 s. Note how differences in IFR and input-output curves emerge relatively rapidly over 1 second indicating a clear and progressive effect of dynamic Cl^- on signalling.