EFFECTS OF INHIBITORY AMINO-ACID ANTAGONISTS ON RECIPROCAL INHIBITORY INTERACTIONS DURING RHYTHMIC MOTOR-ACTIVITY IN THE IN-VITRO NEONATAL RAT SPINAL-CORD

1. The role of inhibitory amino acid transmission in the coordination and generation of rhythmic motor activity was examined with the use of an in vitro neonatal rat spinal cord preparation. Before adding gamma-aminobutyric acid (GABA) or glycine receptor agonists and antagonists, rhythmic motor activity was induced by bath application of acetylcholine (ACh), N-methyl-D,L-aspartate (NMA), or serotonin (5-HT) while monitoring bilateral ankle flexor and extensor electroneurograms (ENGs). The timing of rhythmic flexor and extensor discharge was consistent with that seen during overground locomotion in 27% of 84 bath applications of these substances (n = 65 preparations). 2. Subsequent addition of the GABA(A) receptor agonist muscimol, the GABA(B) receptor agonist baclofen, or glycine, abolished rhythmic activity in 95% of the tested applications. 3. GABA(B) receptor blockade did not disrupt alternating patterns of ENG discharge. However, addition of the GABA(A) receptor antagonist bicuculline, or the glycine receptor antagonist strychnine, transformed alternating flexor-extensor and left-right activity into patterns characterized by bilaterally synchronous rhythmic activation of all hindlimb ENGs. The onset of individual ENG bursts was more abrupt following bicuculline or strychnine. Strychnine also synchronized high-frequency (4-8 Hz) packets of rhythmic discharge within ENG bursts. 4. Some preparations developed synchronous, but unstable, rhythmic activity in the presence of bicuculline or strychnine alone. However, NMA, 5-HT, or ACh was usually required in addition to these antagonists to promote sustained rhythmic activity. 5. The results suggest that 1) GABA(A) and glycine receptor activation may mediate reciprocal left-right and flexor-extensor phase relationships during locomotion, 2) blockade of these receptors facilitates the expression of rhythms dominated by excitatory coupling within the rhythmogenic network, and 3) during rhythmic activity, inhibitory amino acid transmission may influence phasic discharge characteristics but is not essential for generation of the rhythm.