Brain Research, 383 (1986) 353-356 353 Elsevier BRE21795 Remodelling of the neuromuscular junction after subtotal disuse M.A. FAHIM and N. ROBBINS Andrus Gerontology Center and Biological Sciences Department, University of Southern California, Los Angeles, CA 90089-0191 and Department of Developmental Genetics and Anatomy, Medical School, Case Western Reserve University, Cleveland, OH 44106 (U.S.A.) (Accepted 3 June 1986) Key words: Neuromuscular junction - - Nerve terminal - - Synaptic plasticity - - Muscle disuse - - Muscle innervation - - Neuromuscular remodelling Within 5 days after reduction of activity of the rat soleus muscle, there was remodelling of the neuromuscular junction. Post-synap- tic clefts were shorter, wider, and flatter, whereas nerve terminals showed sprouting and longitudinal distortion. The results, which differ from those found after denervation or total disuse, reveal the plasticity of the mature neuromuscular synapse. The response of adult synapses to altered usage can be studied to advantage at the neuromuscular junction (nmj), where the fund of background infor- mation is substantial 15. Total disuse of the mamma- lian nmj rapidly affects both pre- and postsynaptic characteristics 8'11, producing sprouting of termi- nals 2'14, enhanced synaptic transmission 17, and atro- phy of post-synaptic folds 4 and of the perijunctional 'raised area '1° within 3-7 days. Since 100% disuse of any synapse is undoubtedly unphysiological, the question is whether the more naturally encountered situation of incomplete disuse would have similar and equally rapid effects. Previous studies in this area (see below) have dealt mainly with much longer-term events and situations in which extensive electromyo- graphic evidence of the degree of inactivity is lack- ing. One of the best documented forms of neuromuscu- lar disuse, which lasts 2-3 weeks, produces about 90% disuse and does not entail use of drugs or nerve injury, is obtained by limb immobilization 7. Since this procedure causes changes in synaptic transmission within 3-5 days 16, we sought morphologic evidence of synapse remodelling under the same conditions, using both light and scanning electron microscopy (SEM). We describe here a rapid morphological re- sponse to subtotal neuromuscular disuse: it occurs within 5 days and consists of sprouting and longitudi- nal distortion of nerve terminals, flattening of pri- mary grooves and partial loss of peri-junctional sur- face features. These results reveal, in the adult ner- vous system, considerable and rapid synaptic plastici- ty induced by only a brief period of partial disuse. Disuse of the soleus muscle was achieved by unilat- eral pinning of ankle and knee joints at right angles, in anesthetized male 150-180 g Sprague-Dawley rats (Methods in ref. 7). Three and 5 days later, the muscles were removed and prepared for SEM exami- nation 6 or at 5 days, motor nerve terminals were stained with zinc iodide-osmium (ZIO) 1. Morpho- metry with a digitizer was performed on SEM micro- graphs of postsynaptic structures and on camera luci- da drawings of ZIO-stained nerve terminals in teased muscle fibers. In scanning micrographs of control soleus muscles, endplates appeared as raised, smooth plateaux ('raised areas') in which primary clefts were deeply embedded (Fig. 1A), as described in detail else- where 6. At both 3 and 5 days after limb immobiliza- tion, the raised area was reduced by about 33% (5 Correspondence: M.A. Fahim, Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089-0191, U.S.A. 0006-8993/86/$03.50 (~ 1986 Elsevier Science Publishers B.V. (Biomedical Division)