Fig 4. The input-output function of peripherally targeted inhibition is more susceptible to the effects of chloride accumulation than proximally targeted inhibition.

(A) Schematic showing the model where both synaptic excitation and inhibition were located on the distal dendrite. Each synapse provided 5 Hz stochastic input to the neuron. (B) Left, average output firing rate over the 1 s simulation as a function of the number of excitatory synapses for different numbers of peripherally located inhibitory synapses, and where Cl^- was static (dashed lines). Each dot represents the result from 1 simulation (averaged over 3 trials). Increasing the number of inhibitory synapses (shades of blue) offset the neuronal input-output curve to the right (a subtractive operation on the input-output function). Right, allowing [Cl^-]_i to vary in the simulations meant that increasing the number of inhibitory synapses had a reduced ability to offset the input-output curve. (C) Schematic, showing a slightly altered version of the model with synaptic inhibition located on the proximal dendrite. (D) Left, as in ‘B’ but inhibition located proximal to excitatory input, i.e. peri-somatically. With static Cl^-, increasing the number of inhibitory synapses (shades of green) generated divisive gain modulation by both offsetting the threshold and reducing the maximum firing rate of the neuron. Right, output firing rates for the same number of inhibitory synapses were moderately altered with dynamic Cl^-, yet with sufficient numbers of inhibitory synapses complete suppression of output could still be achieved.