Pharmacological Blocking of Spinal GABA Receptors in Monkeys Reduces Sensory Transmission to the Spinal Cord, Thalamus, and Cortex

A century of research established that GABA inhibits proprioceptive inputs presynaptically to sculpt spinal neural inputs into skilled motor output. Recent results in mice challenged this theory by showing that GABA can also facilitate action potential conduction in proprioceptive afferents. Here, we tackle this controversy in monkeys, the most human-relevant animal model, and show that GABA receptors (GABARs) indeed facilitate sensory inputs to spinal motoneurons and interneurons and that this mechanism also influences sensory transmission to supraspinal centers. We performed causal manipulations of GABARs with intrathecal pharmacology in anesthetized monkeys while recording electrical signals in the muscles, spinal cord, thalamus, and cortex. We show that blocking GABARs suppresses spinal reflexes to hand muscles, sensory-evoked single-unit firing in the spinal cord, and sensory-evoked potentials in the thalamus and somatosensory cortex. Our results portray a sophisticated picture of presynaptic modulation of sensory inputs by GABA in the spinal cord.