Effects of target depletion on adult mammalian central neurons: morphological correlates.

The morphological sequelae induced by target removal were studied on adult cat abducens internuclear neurons at both the somata and terminal axon arborization levels. The neuronal target--the medial rectus motoneurons of the oculomotor nucleus--was selectively destroyed by the injection of toxic ricin into the medial rectus muscle. Retrograde labeling with horseradish peroxidase demonstrated the survival of the entire population of abducens internuclear neurons up to one year after target removal. However, soma size was reduced by about 20% three months postlesion and maintained for one year. At the ultrastructural level, a considerable deafferentation of abducens internuclear neurons was observed at short intervals (i.e. 10 days after lesion). Large regions of the plasmalemma appeared devoid of presynaptic boutons but were covered instead by glial processes. The detachment of synaptic endings was selective on abducens internuclear neurons since nearby motoneurons always showed a normal synaptic coverage. By one month, abducens internuclear neurons recovered a normal density of receiving axosomatic synapses. Anterogradely biocytin-labeled axon terminals of abducens internuclear neurons remained in place after the lesion of medial rectus motoneurons, although with a progressive decrease in density. Ultrastructural examination of the oculomotor nucleus 10 days after the lesion revealed numerous empty spaces left by the dead motoneurons. Targetless boutons were observed surrounded by large extracellular gaps, still apposed to remnants of the postsynaptic membrane or, finally, ensheathed by glial processes. At longer intervals (> one month), the ultrastructure of the oculomotor nucleus was re-established and labeled boutons were observed contacting either unidentified dendrites within the neuropil or the soma and proximal dendrites of the oculomotor internuclear neurons, that project to the abducens nucleus. Labeled boutons were never found contacting with the oculomotor internuclear neurons either in control tissue or at short periods after ricin injection. These results indicate that the availability of undamaged neurons close to the lost target motoneurons might support the long-term survival of abducens internuclear neurons. Specifically, the oculomotor internuclear neurons, which likely suffer a partial deafferentation after medial rectus motoneuron loss, constitute a potential new target for the abducens internuclear neurons. The reinnervation of a new target might explain the recovery of synaptic and firing properties of abducens internuclear neurons after medial rectus motoneuron lesion, which occurred with a similar time course, as described in the accompanying paper [de la Cruz R. R. et al. (1994) Neuroscience 58, 81-97.].