PHARMACOLOGICAL CHARACTERIZATION OF THE RHYTHMIC SYNAPTIC DRIVE ONTO LUMBOSACRAL MOTONEURONS IN THE CHICK-EMBRYO SPINAL-CORD

The isolated spinal cord of the chick embryo generates episodes of rhy thmic bursting in which sartorius (hip flexor) and femorotibialis (kne e extensor) motoneurons exhibit characteristic patterns of activity, A t the beginning of each cycle both sets of motoneurons discharge synch ronously, Following this brief synchronous activation sartorius motone uron stop firing at the time of peak femorotibialis activity, producin g a period of alternation between the two sets of motoneurons. Intrace llular recording from motoneurons has suggested that the pause is medi ated by a synaptically induced shunt conductance. However, the pharmac ological basis for this shunt and the nature of the excitatory drive t o motoneurons is unknown, To address these questions we have investiga ted the pharmacology of the rhythmic, synaptic drive to lumbosacral mo toneurons using local and bath application of several excitatory and i nhibitory antagonists, and documenting their effects on motor output i n E10-E12 chick embryos. Local application of bicuculline or picrotoxi n over sartorius motoneurons abolished the pause in firing recorded fr om the sartorius muscle nerve, As a consequence, the pattern of sartor ius and femorotibialis activity was similar and the motoneurons were c oactive, The pause in sartorius firing was shortened following local a pplication of the glycine antagonist strychnine the nicotinic, choline rgic antagonists mecamylamine, and dihydro-beta-erythroidine and sever al excitatory amino acid antagonists, Application of the GABA uptake i nhibitor nipecotic acid depressed the slow potentials and discharge re corded from the sartorius muscle nerve, These findings suggest that th e pause is determined primarily by synaptic inputs acting at motoneuro n GABA(A) receptors with contributions from glycinergic, cholinergic, and glutamatergic inputs. The actions of locally applied GABA onto spi nal neurons are consistent with these findings because the neurotransm itter depolarizes spinal neurons and reduces their input resistance. L ocal application of bicuculline, but not strychnine, onto segments: co ntaining femorotibialis motoneurons altered the amplitude and duration of femorotibialis discharge and changed the profile of the slow poten tials recorded form the muscle nerve, This finding implicates GABAergi c inputs in the regulation of femorotibialis discharge. The pause in s artorius firing was still present and a pause in firing appeared in ea ch cycle of femorotibialis discharge following bath application of bic uculline or strychnine, The pause in both sets of motoneurons could be abolished by local application of the NMDA receptor antagonist AP-5 o nto the motoneurons, but not by local application of bicuculline. This action of AP-5 was in contrast to its activity in normal Tyrode's sol ution where it shortened the pause slightly, These results can be expl ained by hypothesizing an increase in the number of functionally activ e somatic glutamate receptors that can shunt the motoneuron membrane a nd prevent firing. Local application of NMDA or ampa/kainate receptor antagonists depressed discharge in sartorius and femorotibialis motone urons but only when used at high concentration, suggesting that motone uron discharge is regulated by dendritically located excitatory amino acid receptors.