C-FOS EXPRESSION IN THE RAT-BRAIN AFTER UNILATERAL LABYRINTHECTOMY AND ITS RELATION TO THE UNCOMPENSATED AND COMPENSATED STAGES

The expression of the immediate early gene c-fos has been studied in t he entire brain of rats 3, 6 and 24 h after surgical unilateral labyri nthectomy. We combined in situ hybridization for c-fos messenger RNA w ith immunocytochemistry for Fos protein to document very early changes in c-fos expression and to identify with cellular resolution neuronal populations activated by unilateral labyrinthectomy. Three hours afte r unilateral labyrinthectomy a bilateral increase in both c-fos messen ger RNA and protein levels was seen in the superior, medial and spinal vestibular nuclei, nucleus Y, and prepositus hypoglossal nucleus. The se changes were asymmetric in the medial vestibular nucleus, being mos t prominent in the dorsal part of the contralateral nucleus (where sec ond order vestibular neurons are located) and in the ventral part of t he ipsilateral nucleus (where commissural neurons acting on the medial vestibular nucleus of the intact side are located). An increase in c- fos messenger RNA expression was seen bilaterally, but with an ipsilat eral predominance, in the vermal and paravermal areas of the cerebella r cortex, flocculus and paraflocculus, as well as in the precerebellar lateral and paramedian reticular nuclei. c-fos messenger RNA and prot ein levels increased in a few regions of the contralateral inferior ol ive. A predominantly ipsilateral increase in c-fos expression also occ urred in the caudate-putamen. A bilateral but not exactly symmetric in crease in both c-fos messenger RNA and protein levels was present in s everal nuclei of the dorsal pontine tegmentum (parabrachial nucleus, l ocus coeruleus and laterodorsal tegmental nucleus), mesencephalic peri aqueductal gray, and several hypothalamic, thalamic and cerebrocortica l regions. No change was seen in the cerebellar nuclei, lateral vestib ular nucleus and red nucleus. The increased expression of c-fos observ ed 3 h after unilateral labyrinthectomy, in conjunction with the sudde n occurrence of postural and motor deficits, usually declined 6-24 h a fter the lesion, i.e. during the development of vestibular compensatio n. In the dorsal part of the medial vestibular nucleus, however, the p attern of c-fos expression observed 3 h after unilateral labyrinthecto my was reversed 6-24 h after the lesion: both c-fos messenger RNA and protein levels increased on the ipsilateral side, but greatly decrease d on the contralateral side. In conclusion, asymmetric changes in c-fo s expression occurred within 3 h after unilateral labyrinthectomy, but gradually declined or reversed 6 and 24 h after the lesion, thus bein g temporally related to the appearance and development of vestibular c ompensation.