Response of abducens internuclear neurons to axotomy in the adult cat

The highly specific projection of abducens internuclear neurons on the medi al rectus motoneurons of the oculomotor nucleus constitutes an optimal mode l for investigating the effects of axotomy in the central nervous system. W e have analyzed the morphological changes induced by this lesion on both th e cell bodies and the transected axons of abducens internuclear neurons in the adult cat. Axotomy was performed by the transection of the medial longi tudinal fascicle. Cell counts of Nissl-stained material and calretinin-immu nostained abducens internuclear neurons revealed no cell death by 3 months postaxotomy. Ultrastructural examination of these cells at 6, 14, 24, and 9 0 days postaxotomy showed normal cytological features. However, the surface membrane of axotomized neurons appeared contacted by very few synaptic bou tons compared to controls. This change was quantified by measuring the perc entage of synaptic coverage of the cell bodies and the linear density of bo utons. Both parameters decreased significantly after axotomy, with the lowe st values at 90 days postlesion (similar to 70% reduction). We also explore d axonal regrowth and the possibility of reinnervation of a new target by m eans of anterograde labeling with biocytin. At all time intervals analyzed, labeled axons were observed to be interrupted at the caudal limit of the l esion; in no case did they cross the scar tissue to reach the distal part o f the tract. Nonetheless, a conspicuous axonal sprouting was present at the caudal aspect of the lesion site. Structures suggestive of axonal growth w ere found, such as large terminal clubs, from which short filopodium-like b ranches frequently emerged. Similar findings were obtained after parvalbumi n and calretinin immunostaining. At the electron microscopy level, biocytin -labeled boutons originating from the sprouts appeared surrounded by either extracellular space, which was extremely dilated at the lesion site, or by glial processes. The great majority of labeled boutons examined were, thus , devoid of neuronal contact, indicating absence of reinnervation of a new target. Altogether, these data indicate that abducens internuclear neurons survive axotomy in the adult cat and show some form of axonal regrowth, eve n in the absence of target connection. (C) 2000 Wiley-Liss, Inc.