Electrical stimulation of hindlimb increases neuronal cell death in chick embryo

Abstract

The daily treatment of chick embryos with neuromuscular blocking agents during the period of massive naturally occurring death of spinal motoneurones (days 5–10) reduces the normal loss of these cells^1,2. Because both pre- and postsynaptic blocking agents have this effect³, the cause seems to be related to a reduction in synaptic and/or muscular activity. If this interpretation is correct, an experimentally induced increase in nerve or muscle activity (and/or an increased activation of acetylcholine receptors, AChR), during the normal cell death period should accelerate or enhance the loss of motoneurones. Consistent with this prediction, we have found that daily treatment with the nicotinic receptor agonist, carbachol, or with the anti-cholinesterase (anti-ChE) agent, eserine, leads to a significant enhancement of cell death of spinal motoneurones³. However, because in the same study other related agents (for example nicotine) failed to alter normal cell death, we believed that a different approach might provide a better test of our prediction. We now report that short-term continuous electrical stimulation of the hindlimb (the musculature and nerve trunks) initiated at any time between stages 31 (day 7) and stage 34 (day 8) results in a significant reduction in the number of healthy motoneurones and an increase in the number of pyknotic (degenerating) motoneurones in the lumbar lateral motor column (LMC). As the number of pyknotic cells in the dorsal root ganglia (DRG) is unaltered, this effect seems to be specific to motoneurones.