Reducing transmitter release from nerve terminals influences motoneuron survival in developing rats.
Motoneurons in neonatal rats die following injury to the peripheral nerve. However, this vulnerability to nerve injury declines rapidly so that nerve injury at five days of age results in little if any motoneuron death. We have proposed that the role of the target during this critical period of development is to up-regulate the release of transmitter from developing motor nerve terminals. Here we show that reducing the release of acetylcholine from nerve terminals in neonatal rats can affect motoneuron maturation and survival. The soleus muscle in neonatal rats was treated with either magnesium or hemicholinium, and the number of motoneurons that survived was established 10 weeks later by retrograde labelling. Following treatment with magnesium, only 58.1% (+/-10.4 S.E.M., n=5) of the motoneurons in the soleus motor pool survived, although hemicholinium had no effect on motoneuron survival. However, those motoneurons that survived following treatment with either magnesium or hemicholinium did not develop normally since they remained susceptible to axotomy-induced cell death for longer than normal. In adult animals in which the sciatic nerve was crushed at five days of age following prior treatment with either magnesium or hemicholinium, only 27.6% (+/-6.2 S.E.M., n=5) and 44% (+/-6.1 S.E.M., n=4) of motoneurons in the sciatic motor pool survived, respectively, although no motoneurons died following injury alone or when injury was preceded by treatment with control implants containing NaCl. These results indicate that the release of acetylcholine from motor nerve terminals plays an important role in the development and survival of motoneurons.
Greensmith
L
L
Sobell Department of Neurophysiology, Institute of Neurology, Queen Square, London, UK. l.greensmith@ion.ucl.ac.uk
Ng
P
P
Mohaghegh
P
P
Vrbová
G
G
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D000870:Anterior Horn Cells / Q000166:cytology* / Q000502:physiology*; D001370:Axonal Transport; D002470:Cell Survival; D005260:Female; D006426:Hemicholinium 3 / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development* / Q000294:innervation; D009409:Nerve Crush; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000254:growth & development / Q000502:physiology*
D006426:Hemicholinium 3; D008274:Magnesium; D000109:Acetylcholine