INVOLVEMENT OF GLYCINE AND GABA(A) RECEPTORS IN THE PATHOGENESIS OF SPINAL MYOCLONUS - IN-VITRO STUDIES IN THE ISOLATED NEONATAL RODENT SPINAL-CORD

Studies of pathogenetic mechanisms of myoclonus and spinal spasticity have established a strong association between deficient inhibitory gly cinergic transmission and pathologic rigidity and tremor. Consistent w ith known cases in the clinical literature, electrophysiologic data fr om animal models of myoclonus implicate dysfunction of segmental spina l cord circuitry. The present study sought to further explore pathogen etic mechanisms at the circuit level. In vitro preparations of isolate d spinal cord from neonatal rodents allowed for stable recordings of i ndividual cells as well as populations of motoneurons. Blockade of gly cine receptors enhanced 5- to 15-Hz sinusoidal oscillations that were synchronous in entire populations of motoneurons as well as along mult iple segments of the spinal cord. Oscillations at motoneurons were med iated largely by non-NMDA excitatory synaptic inputs. Blockade of GABA (A) receptors, and not GABA(B) receptors, abolished sinusoidal oscilla tions, suggesting a critical role for GABA, receptors in the premotone uronal circuitry responsible for generation or transmission of the sin usoidal oscillations. These data offer new insights into possible path ogenetic mechanisms of spinal myoclonus and may help guide future rese arch leading to specific therapies for hyperkinetic movement disorders of spinal origin.