Embryonic expression of motoneuron topography in the rat diaphragm muscle.

The phrenic motoneuron pool of the rat projects onto the diaphragm muscle with a distinct rostrocaudal bias. This bias is detectable at birth and is reestablished following denervation. In an effort to define the mechanisms underlying this topographic bias, we asked whether growing phrenic motoneurons select their muscle contacts initially upon first contact or whether the initial neuromuscular distribution is random, to be specified later through synaptic rearrangement. The onset of neurotransmission in embryonic diaphragm muscles aged E-14 to E-18 was studied using focal extracellular microelectrodes. Two important phenomena were observed. First, motoneurons from all three cervical ventral roots (C4, C5, and C6) establish functional innervation at the same time. Second, already at E-15, when the earliest synaptic potentials could be recorded, a distinct rostrocaudal bias was detected. This bias was amplified as innervation progressed to rostral and caudal sectors during E-16 to E-18. These results suggest that growing phrenic motoneurons make topographic choices as they navigate toward their muscle targets. Moreover, the results indicate that further research into the mechanisms for topographic selectivity should focus on initial nerve-muscle contacts in the embryo, rather than secondary processes of error correction.