Non-synaptic modulation of dorsal column conduction by endogenous GABA in neonatal rat spinal cord

Abstract

GABA a receptor activation can modulate axonal conduction in the isolated dorsal column of the neonatal rat spinal cord in vitro. However, it is not known whether axonal conduction in the dorsal column can be modulated by endogenous GABA in the developing spinal cord. We consequently compared the effects of GABA, a GABA a agonist, and a GABA uptake inhibitor on axonal conduction in the dorsal column of hemisected neonatal (0- to 9-day-old) rat spinal cords in vitro. Extracellular compound action potentials evoked by supramaximal stimuli were recorded at two points with glass microelectrodes. GABA (10 −4 to 10 −3 M) reversibly decreased the compound action potential amplitude and the population conduction velocity. At 10 −4 M, compound action potential amplitudes fell by 45.0±6.5% of control while the conduction velocity slowed by 11.8±4.3% ( n=5). The GABA a receptor agonist, isoguvacine, mimicked the effects of GABA on the dorsal column compound action potential. In contrast, while GABA at 10 −5 M decreased the amplitude by 7.7±3.1%, it increased conduction velocity by 9.7±1.3% ( n=5). The GABA uptake inhibitor, nipecotic acid (10 −3 M), consistently decreased the compound action potential amplitude by 17.7±6.5% ( n=6) but the conduction velocity slowed in four out of six preparations. In two instances, nipecotic acid decreased the amplitude and increased the conduction velocity. The effects of nipecotic acid on the dorsal column compound action potential were blocked in the presence of the GABA a antagonist bicuculline. Finally, nipecotic acid had no effect on the hemicord after an incubation with nipecotic acid to eliminate endogenous GABA in the hemicord. These results indicate that endogenous GABA can modulate axonal conduction of the dorsal column by activating GABA a receptors in the neonatal rat spinal cord. While the biological role of interaction of GABA and GABA a receptors in the dorsal column is not apparent, these results support the hypothesis that axonal conduction in long tracts of the spinal cord is subject to non-synaptic modulation through endogenous release of GABA.