Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn

  1. Kwan Yeop Lee
  2. Stéphanie Ratté
  3. Steven A Prescott  Is a corresponding author
  1. The Hospital for Sick Children, Canada
  2. University of Toronto, Canada
8 figures and 1 additional file

Figures

Disinhibition causes receptive fields to expand.

(A) Cartoon depicts how narrowly tuned excitation combined with broadly tuned inhibition produces a receptive field (RF) with an excitatory center and inhibitory surround. (B) Firing rate histograms …

Units recorded in vivo can be divided into two groups.

(A) Spike waveforms were separated according to their monophasic (blue) or biphasic (red) shape. (B) Units subdivided by spike waveform also differed in their adaptation pattern, as illustrated by …

Adapting and non-adapting units correspond to excitatory and inhibitory neurons, respectively.

(A) Sample firing rate histograms from a typical adapting unit (blue) and non-adapting unit (red) during brush stimulation (bars) before and after intrathecal application of 200 μM …

Figure 4 with 1 supplement
Adapting and non-adapting units are differentially affected by KCC2 blockade.

(A) Input-output (i–o) curves show firing rate evoked by increasing force applied by von Frey hairs to the RF surround in a typical adapting unit (blue) and non-adapting unit (red) before and after …

Figure 4—figure supplement 1
Intrathecal strychnine (50 μM) had no significant effect on the rate of spontaneous firing in non-adapting units (T9 = 1.65, p=0.13; paired t-test).
Excitatory and inhibitory neurons have equivalent chloride extrusion capacity.

(A) Responses to 5–10 ms-long puffs of 1 mM GABA (arrowhead) were measured in voltage clamp at different holding potentials (inset) in neurons patched with a high-chloride (25 mM) pipette solution. …

Figure 6 with 1 supplement
Excitatory and inhibitory neurons are differentially affected by virtual disinhibition.

(A) Cartoon depicts dynamic clamp experiments: noisy excitatory and inhibitory conductances were generated through separate Ornstein-Uhlenbeck processes, converted to currents based on recorded …

Figure 6—figure supplement 1
Effects of virtual disinhibition for α = 0.5 (virtual stimulation in RF centre).

(A) Average i-o curves (± sem) for excitatory neurons (blue) and inhibitory neurons (red). (B) Einh had a significant effect on slope (F1,13 = 8.82, p=0.011, two-way repeated measures ANOVA) but …

BDNF causes disinhibition in both adapting and non-adapting units.

(A) Intrathecal BDNF (70 µg) and ACTZ (10 mM) had a significant effect on the firing evoked by brush stimulation of the RF center (F2,56 = 15.41, p<0.001; two-way repeated measures ANOVA) or …

KCC2 blockade unmasks significantly more excitation in adapting units than in non-adapting units.

(A) Stimulation of the RF center (Scenter) evokes net excitation whereas stimulation of the RF surround (Ssurround) normally evokes net inhibition but evokes excitation after KCC2 blockade. (B) …

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