Final Acceptred Version Jn-00735-2005.r2 Rhythmic Neuronal Discharge in the Medulla and Spinal Cord of Fetal Rats in the Absence of Synaptic Transmission

Spontaneous rhythmic neuronal activity is generated in the developing vertebrate nervous system. The patterned activity spreads diffusely throughout the fetal neuraxis. Here we demonstrate the ability of the fetal rat spinal cord and medulla to generate and transmit robust rhythmic patterns in the absence of synaptic activity. Regular rhythmic discharges were produced by fetal tissue bathed in low or zero [Ca]o solution. The activity persisted in the presence of antagonists to neurotransmitter receptors that are known to mediate synapticmediated events associated with fetal rhythms. A combination of ventral root recordings and optical imaging using voltage-sensitive dyes demonstrated the extensive spread of rhythmic discharge in spinal cord and medullary neuronal populations of in vitro preparations. Whole-cell recordings from medullary slices were performed to examine the ionic conductances and revealed the importance of persistent sodium conductances for generation of rhythmic activity in hypoglossal (XII) motoneurons. Rhythmic bursting in XII motoneurons persisted in the presence of gap junction blockers, although the amplitude of synchronized motor discharge recorded from nerve roots was diminished. We propose that non-synaptically mediated conductances, potentially via extracellular ionic flux and/or ephaptic and electrotonic interactions mechanisms, act in concert with neurochemical transmission and gap junctions to promote the diffuse spread of rhythmic motor patterns in the developing nervous system.