Influence of reduced neuron pool on the magnitude of naturally occurring motor neuron death

Abstract

The present investigation was undertaken to examine the role of peripheral competition in survival of motor neurons during development. A loss of approximately half of the trochlear motor neurons in duck and quail occurs during the course of normal embryogenesis. The number of motor neurons in the nucleus of quail prior to the onset of cell death is identical to the final number of survivors in the nucleus of duck embryos (about 1,300 neurons). In the present study competition at the peripheral target was decreased by reducing the number of trochlear motor neurons initially projecting to their target muscle. This was accomplished by substituting the midbrain of duck embryos with the same neural tissue from quail embryos. Midbrain transplantation was performed before motor axon outgrowth and normal cell death begin. The development of the motor neurons and their sole target of innervation, the superior oblique muscle, was examined by using a variety of techniques. The source of the grafted motor neurons and of a reduction in the size of the motor neuron pool was confirmed from histological sections and cell counts. The grafted motor neurons projected their axons into the appropriate peripheral target, which was determined by the use of HRP tracing technique. Counts of muscle fibers, motor endplates, and acetylcholine receptors and measurement of total muscle protein indicated that the size of the superior oblique muscle in the chimera embryos was similar to that of the normal duck but significantly larger than the muscle in quail embryos. Electrophysiological observations indicated that the grafted trochlear motor neurons made functional connections with the superior oblique muscle. Counts of the trochlear motor neurons after the period of cell death indicated an average of 1,310 neurons in the nucleus of duck, 772 in quail, and 690 in the chimera embryos. The number of motor neurons in the chimera embryos is not significantly different from that in the normal quail. In other words, in spite of reduced peripheral competition trochlear motor neuron death of normal magnitude occurred. Lack of increased cell survival in our study suggests that trochlear motor neurons do not compete for survival at the peripheral target.

The relationship of intramuscular nerve branching and synaptogenesis to motoneuron survival

“…Increasing the size of the target rescued some limb-innervating motoneurons from death (Hollyday and Hamburger, 1976;see also O'Brien and Oppenheim, 1990; for thoracic motoneurons), and decreasing the size of the "competing" neuronal population in frog spinal cord (Olek and Edwards, 1978), in a specific chick motoneuron pool ( Lance-Jones and , and in the chick ciliary ganglion (Pilar, Landmesser, and Burstein, 1980), all resulted in increased survival of the remaining neurons. However, because the alteration in neuronal survival often did not quantitatively match that predicted by the most simple version of the numericalmatching hypothesis (Pilar et al, 1980;Tanaka and Landmesser 1986b;Sohal et al, 1986Sohal et al, , 1991, this hypothesis and the importance of the target in neuronal survival has more recently been called into question.…”

The role of target size in neuronal survival

“…For example, Lamb ( 1980) observed no difference in the final number of spinal motor neurons when both sides of the spinal cord innervated a single hindlimb in Xenopus. We were also unable to save any additional quail trochlear motor neurons when they innervated the larger target muscle of the duck (Sohal et al, 1986). Similarly, Tanaka and Landmesser ( 1986) reported that no additional quail motor neurons were rescued when quail spinal cord innervated the larger chick limb.…”

“…The effect of a larger than normal size target on neuron survival was examined by making the smaller trochlear motor neuron pool of the quail embryo innervate the larger superior oblique muscle of the duck embryo (Sohal et al, 1986). This was accomplished by grafting midbrain, the embry-onic source of trochlear nucleus, of quail in the place of the midbrain of the duck embryo.…”

Synapse formation on quail trochlear neurons transplanted in duck embryos before naturally occurring motor neuron death

“…In view of our finding that the synapses in chimera embryos develop in a fashion similar to that of the duck it is necessary to discuss the new information at hand with respect to the results on motor neuron survival reported previously. 21 As was pointed out in the introduction, our earlier studies determined that when quail trochlear motor neurons innervated a larger duck superior oblique muscle we were unable to rescue quail cells from natural cell death. The results of this investigation indicate that the afferent synapses for these motor neurons were different.…”