Fos-protein expression in noradrenergic locus coeruleus neurons after unilateral labyrinthectomy in the rat.

Abstract

c-Fos mRNA and the related Fos-protein are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation and plasticity. In a recent study (14), we found that rats submitted to unilateral labyrinthectomy (UL) displayed an asymmetric increase in the expression of both c-fos and Fos-protein not only in several vestibular, precerebellar and cerebellar structures and the caudate-putamen, but also in the locus coeruleus (LC)-complex, whose neurons integrate labyrinthine signals and are apparently involved in the plastic changes which are at the basis of vestibular compensation. In the present study we investigated the putative noradrenergic nature of the Fos-positive LC neurons observed after UL by combining Fos-protein immunocytochemistry with the immunocytochemical detection of tyrosine hydroxylase (TH), a synthetizing enzyme of noradrenaline. The experiments were performed in rats sacrificed 3, 6 and 24 h after surgical lesion of one labyrinth. The results obtained were in agreement with the previous findings, showing that already 3 h after UL an asymmetric increase of the c-fos and/or Fos-protein expression occurred in the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen. Most interestingly, the Fos-protein expression markedly increased in the LC-complex of both sides, although mainly ipsilaterally to the intact side. It appeared also that several Fos-positive LC-complex neurons were probably noradrenergic in nature, as they could be double-labeled with the Fos/TH technique. These findings were attenuated 6 h after UL and disappeared after 24 h, when partial compensation of the vestibular syndrome had occurred. Thus, UL results in asymmetric functional activation in the LC region of well identified noradrenergic neurons. This finding is attributed to the fact that asymmetric stimulation of labyrinth receptors gives rise to asymmetric changes in firing rate of LC neurons (45). Since these neurons send noradrenergic afferents to several target structures such as the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen, we postulated that the asymmetric labyrinthine activation of the noradrenergic LC system, occurring after UL, could increase the Fos-protein expression in the above mentioned brain structures. This possibility could then represent a key factor in determining the plastic changes, which are at the basis of vestibular compensation.