Role of GABA A inhibition in modulation of pyramidal tract neuron activity during postural corrections

Abstract

In a previous study we demonstrated that the activity of pyramidal tract neurons (PTNs) of the motor cortex is modulated in relation to postural corrections evoked by periodical tilts of the animal. The modulation included an increase in activity in one phase of the tilt cycle and a decrease in the other phase. It is known that the motor cortex contains a large population of inhibitory GABAergic neurons. How do these neurons participate in periodic modulation of PTNs? The goal of this study was to investigate the role of GABA(A) inhibitory neurons of the motor cortex in the modulation of postural-related PTN activity. Using extracellular electrodes with attached micropipettes, we recorded the activity of PTNs in cats maintaining balance on a tilting platform both before and after iontophoretic application of the GABA(A) receptor antagonists gabazine or bicuculline. The tilt-related activity of 93% of PTNs was affected by GABA(A) receptor antagonists. In 88% of cells, peak activity increased by 75 +/- 50% (mean +/- SD). In contrast, the trough activity changed by a much smaller value and almost as many neurons showed a decrease as showed an increase. In 73% of the neurons, the phase position of the peak activity did not change or changed by no more than 0.1 of a cycle. We conclude that the GABAergic system of the motor cortex reduces the posture-related responses of PTNs but has little role in determining their response timing.

Fig. 1

Experimental design. (A) The cat stood on a platform. A mechanical sensor P measured displacements of the body in relation to the platform (postural corrections). (B) When the platform was tilted to the right, the cat kept the dorsal-side-up orientation by extending the limbs on the right side. A mechanical sensor measured the angular displacement of the platform (Tilt). (C) A system for recording the activity of PTNs and for iontophoretic application of gabazine or bicuculline. A two- or three-channel glass pipette was attached to an extracellular microelectrode. Not shown to scale. (D) The electrode and pipette were inserted into the motor cortex by a miniature microdrive attached to the head. (E) PTN activity was recorded along with platform tilts and postural corrections; R, right; L, left.

Fig. 2

A representative example of the effect of gabazine and bicuculline on postural responses of a PTN. A raster and histogram of the PTN activity during 80 tilt cycles are shown for each of the following conditions: Control, before application; Gabazine, 2 min after gabazine application (20 mm, 100 nA, 100 s); Recovery 1 is 15 min after gabazine application; Bicuculline, 3 min after bicuculline application (20 mm, 100 nA, 100 s). Recovery 2 is 15 min after bicuculline application. Note the significant increase in peak activity in both Gabazine and Bicuculline tests while the rest, trough activity and timing of activity did not change. Fmax and Fmin, the maximum and minimum frequencies in the histogram; ΔFmax = Fmax − Frest; ΔFmin = Frest − Fmin.

Fig. 3

Maximum activity (Fmax) of individual PTNs under (A) Gabazine vs. Bicuculline, and (B) in Control vs. Recovery. In A and B, • denotes a PTN whose activity was statistically significantly different in the two conditions; ○, those whose activity was not significantly different.

Fig. 5

Effects of GABA_A receptor antagonists on PTN population activity: Frest, Fmax and Fmin. *P < 0.01 for the increase in Fmax after treatment with a GABA_A receptor antagonist.

Fig. 4

Effects of GABA_A receptor antagonists on the activity of individual PTNs during postural corrections. (A) Effect on the rest activity of the neurons (Frest). (B) Effect on the maximum activity of the neurons (Fmax). (C) Effect on the minimum activity of the neurons (Fmin). (D) Effect on the difference between Frest and Fmax (ΔFmax). (E) Effect on the difference between Frest and Fmin (ΔFmin). In A–E, • denotes a PTN whose activity was statistically significantly different in the two conditions; ○, those whose activity was not significantly different.

Fig. 6

Effects of GABA_A receptor antagonists on (A) the coefficient of modulation and (B) the phase of maximum activity of individual PTNs. In A and B, • denotes a PTN whose activity was statistically significantly different in the two conditions; ○, those whose activity was not significantly different.