Genetically-associated variations in the development of reflex movements and synaptic junctions within an early reflex pathway of mouse spinal cord.

The embryonic development of reflex forelimb movements produced by cutaneous stimulation of the forepaw was examined in five inbred strains of the house mouse, Mus musculus. A quantitative electron microscopic study of synapse formation between the neurons that comprise the spinal cutaneous reflex arc was also carried out on specimens from three of the strains subjected to reflex testing. This investigation provides evidence that there is significant genetically-associated variability in the developmental timing of synapse formation within this disynaptic pathway and in the reflex behavior which it mediates. Specifically, it was found that C57BL/6J embryos had greater numbers of synaptic junctions in the reflex pathway at embryonic days 14-16, and they also showed reflex movements earlier than LP/J embryos. C57BL/6J embryos also showed a more rapid increase in the number of boutons during this embryonic period. CBA/CaJ embryos displayed a temporal pattern of development that differed from both C57BL/6J and LP/J. At E15, CBA/CaJ embryos were more similar to LP/J with regard to both reflex activity and synapse number, but by E16, CBA/CaJ values for both of these measures were more similar to C57BL/6J. On the basis of the data detailed in the text, we suggest that the strains differ in the following manner: C57BL/6J embryos develop boutons rapidly but appear to be relatively inefficient in the actual formation of synaptic junctions; CBA/CaJ embryos develop boutons at a slower rate than C57BL/6J but form synaptic junctions more efficiently; LP/J embryos develop boutons slowly and are also relatively inefficient in forming synaptic junctions. The genetic implications of--and some developmental processes which might be responsible for--the observed strain differences in the timing of synaptic development are discussed in the text. There was no detectable genetic variability of the basic sequence in which the neurons of the cutaneous reflex arc develop their synaptic connections. For all three strains examined, the data indicated that synaptic closure occurred in a retrograde sequence with respect to the direction that neurotransmission normally flows between the neurons of this pathway. This finding agrees with results obtained by other investigators from a number of diverse vertebrate species, and such a widespread lack of variability implies that a retrograde sequencing of synapse formation is involved in the development of specific neuronal connectivities.