PRESYNAPTIC GABA-A AND GABA-B RECEPTOR-MEDIATED PHASIC MODULATION IN AXONS OF SPINAL MOTOR INTERNEURONS

The lamprey spinal cord has been utilized to investigate the role of presynaptic inhibition in the control of the spinal motor system. Axons of the lamprey spinal cord are comparatively large because of their lack of myelination. Axons impaled with microelectrodes demonstrate depolarizing responses to the application of GABA(A) and GABA(B) receptor agonists, muscimol and baclofen. These depolarizing effects are counteracted by the specific GABA(A) and GABA(B) receptor antagonists, bicuculline and phaclofen. GABA(A) receptor activation leads to a gating of Cl- channels on the axons. However, the ionic mechanism leading to axonal depolarization following GABA(B) receptor activation is unknown. After initiation of fictive locomotion, these axons demonstrate oscillations in axonal membrane potential related to the locomotor cycle. During ficitive locomotion they depolarize in phase with the bursting of the ipsilateral ventral root of the same segment. These axonal membrane potential oscillations are due to a phasic GABA(A) and GABA(B) receptor-mediated gating of ion channels on the axonal membrane. Fictive locomotion in the lamprey spinal cord is largely unaffected by antagonism of one or other GABA receptor subtype alone, but is severely disrupted by simultaneous antagonism of both subtypes. In conclusions, we demonstrate, for the first time, an agonist-gated depolarization of a vertebrate presynaptic element measured by direct impalement of the axon under study. We also demonstrate that GABA-mediated presynaptic inhibition occurs in axons of spinal interneurons. It is not limited to the primary afferents as has previously been believed.