Critical periods in rat motoneuron development.

Reinnervation of rat internal intercostal muscles was examined 2 weeks after intramuscular axotomy in the period embryonic Day 17 (E17) to postnatal Day 2 (PN2). The efficiency of reinnervation depended on the day of denervation. Responses to nerve stimulation were common only in muscles denervated in the interval E19-21. Functional reinnervation was seldom seen in muscles denervated earlier, and was absent in muscles denervated shortly after birth. We suggest that there are "critical periods" in the sequence of differentiation of motoneurons. At E17 these neurons are very susceptible to cell death and any that lose contact with their muscle will die. Motoneurons axotomized later, while motor unit size is still increasing, can regenerate some functional nerve-muscle junctions. Motor unit size reaches its maximum by E21 and if motoneurons are axotomized after that time, in neonates, they cannot form more synaptic terminals although they can still extend axons. During this early postnatal period motoneurons normally reduce their number of nerve-muscle contacts. Finally, at 3 weeks of age, motoneurons reach their adult state when they are capable of regeneration relatively unhindered by restrictions on the number and location of their peripheral connections.