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Figure 2 | Molecular Pain

Figure 2

From: Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain

Figure 2

Reduction of E anion compromises inhibitory control of firing rate. Output firing rate (f out) is plotted against the total rate of EPSPs received from all presynaptic neurons (f exc) for different values of E anion tested at 5 mV increments from -70 mV (purple) to -45 mV (orange). The f out-f exc curve for no inhibition (α = 0) is shown as a thick black line on each panel. Parts A-C are based on simulations in the basic model. (A) With proportional inhibition, f inh = α f exc. Each panel shows results for a different value of α. Divergence of the colored curves increases as α increases. (B) Feedback inhibition was added to proportional inhibition with α = 0.5. Incorporating feedback inhibition had much the same effect as increasing α under conditions with pure proportional inhibition (see part A) except that, with feedback inhibition, the increased divergence of the colored f out-f exc curve was particularly pronounced for E anion = -50 and -45 mV. This is because those values of E anion cause paradoxical excitation, meaning feedback inhibition actually becomes feedback excitation (i.e. a positive feedback loop), which makes for an extremely hyperexcitable system. (C) The final two panels show constant inhibition (i.e. f inh is independent of f exc). Under these conditions, the f out-f exc curves tend to remain parallel rather than diverge with increasing f exc, but increasing f inh nonetheless increases the vertical spacing of those curves. Comparing across parts A-C shows that reduction of E anion has a similar effect on inhibitory control of firing rate for all three conditions. The f out-f exc curves for E anion = -50 and -45 mV (yellow and orange) exhibit paradoxical excitation since they lie above the f out-f exc curve for no inhibition (black). The f out-f exc curve for E anion = -55 mV (light green) exhibits complete disinhibition since it lies very close to the f out-f exc curve for no inhibition. The f out-f exc curves for E anion = -60 and -65 mV (dark green and blue) exhibit modest disinhibition since they lie below the f out-f exc curve for no inhibition but above the f out-f exc curve for E anion = -70 mV (purple). Based on proportional inhibition with α = 1, simulations were repeated in the tonic-spiking model (D) and in the single-spiking model (E). Although the f out-f exc curves vary between cell types (compare also with basic model in part A), the more important comparison is between curves for different E anion within a specific cell type: in the basic and tonic-spiking models, reduction of E anion to -55 mV causes complete disinhibition, while complete disinhibition in the single-spiking model seems to require a slightly greater reduction, to around -50 mV.

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