Figure 4. Tonic chloride conductance and extrusion capacity determine somatic $E_{GABA}$ and SNr responses to simulated 40 Hz GPe stimulation.

(A) Dependence of somatic $E_{GABA}$ on the tonic chloride conductance ($g_{GABA}^{Tonic}$) and the potassium-chloride co-transporter KCC2 extrusion capacity ($g_{KCC2}$). (B–E) Examples of SNr responses to simulated indirect pathway stimulation at different positions in the 2D ($g_{GABA}^{Tonic}$,$g_{KCC2}$) parameter space, as labeled in panel (A). (E1 and E2) Notice the two distinct types of partial inhibition. Inset highlights the drift in $E_{GABA}$ during stimulation.

Figure 4—figure supplement 1. Biphasic SNr response to longer simulated GPe stimulation.

(A) Dependence of somatic $E_{GABA}$ on the tonic chloride conductance ($g_{GABA}^{Tonic}$) and the potassium-chloride co-transporter KCC2 extrusion capacity ($g_{KCC2}$) as previously shown in Figure 4A. (B) Example of ‘Partial Inhibition’ in response to 1 s of stimulation resulting due to a small accumulation of intracellular $C{l}^{-}$, as shown in Figure 4E2. (C) Example of longer 10 s stimulation resulting in larger $C{l}^{-}$ accumulation resulting in a transition of $E_{GABA}$ from inhibitory to excitatory and thus causing a biphasic response in a simulated SNr neuron’s firing rate, as seen in 10 s stimulation experiments. $g_{GABA}^{Tonic}$ and $g_{KCC2}$ are the same in (B) and (C) and take the values indicated in (A). To generate the biphasic example the synaptic conductance $g_{GABA}^S$ was increased from 0.2 to 0.4 nS/pF.