GABAergic inactivation of the central pattern generators for locomotion in isolated neonatal rat spinal cord

Abstract

1. Experiments were performed using an isolated brainstem-spinal cord preparation from newborn rats, in order to study the GABAergic control of the spinal neuronal networks that generate locomotor rhythms in mammals. Locomotor-like activities were recorded in the ventral roots, and the various neurochemical compounds were added to the superfusion saline. 2. Bath application of GABA suppressed in a dose-dependent manner the motor activity induced by an excitatory amino acid N-methyl-D,L-aspartate (NMA). Both the GABAA agonist muscimol and the GABAB agonist baclofen mimicked the effects of GABA, since they either slowed down or stopped the rhythmic activity. 3. Experiments were performed in which the lumbar compartment was superfused separately from the brainstem. Chemical activation of the brainstem by NMA alone failed to induce locomotor-like activity. When GABAA (bicuculline) and GABAB (phaclofen) antagonists were simultaneously bath applied to the lumbar spinal cord, however, locomotor-like activity was induced. 4. The GABA uptake inhibitors nipecotic acid and guvacine suppressed the rhythmic motor pattern induced by NMA in a dose-dependent manner. The effects of nipecotic acid were reversed by bicuculline and phaclofen. 5. Bicuculline added during NMA-induced locomotor-like activity greatly increased both the frequency and amplitude of motor bursts, while phaclofen modified only the frequency. 6. The motor pattern depended on the balance between activatory and inactivatory influences, since the rhythmic patterns recorded with low doses of NMA associated with high doses of bicuculline were similar to those elicited by higher doses of NMA associated with low doses of bicuculline.(ABSTRACT TRUNCATED AT 250 WORDS)