gms | German Medical Science

Introduction: Electrical intracochlear stimulation evokes expression of immediate-early genes, such as c-Fos, in the mammalian auditory brainstem. Both c-Fos and ATF2 proteins are monomers of the heterodimeric activator-protein-1 (AP-1) transcription factor complex (Fos:Jun or ATF2:Jun, respectively). AP-1 triggers the expression of genes associated with neuronal growth and plasticity. Earlier studies show that different spatio-temporal patterns of c-Fos expression depend on hearing experience. Further investigation is needed to identify the dynamics and changes in expression patterns of pATF2, which constitutes a competing monomer for c-Fos.

Methods: Normal hearing and neonatally deafened (hearing threshold 92 ± 8.77dB above normal hearing threshold) Wistar rats were unilaterally stimulated with a cochlear implant (CI) for 45 min, 73 min or 2 h. Using c-Fos and pATF2 immunhistochemistry, the number of positive neurons was evaluated for the ventral cochlear nucleus (VCN) and the lateral superior olive (LSO).

Results: With increasing stimulation time, c-Fos expression rose in ipsilateral VCN and LSO in both hearing and deaf rats. For all stimulation intervals, c-Fos expression in deaf rats was significantly higher than in hearing rats (p>0.001). Remarkably, both groups showed the qualitatively identical effect: A pATF2 decrease is spatio-temporally correlated with the increase in c-Fos expression in VCN and LSO.

Conclusions: Like a hearing brain, a neonatally deafened brain can respond to changing activity patterns in the auditory nerve. After monaural stimulation with a CI, changes in gene expression were observed in activated auditory neurons. These changes result in a shift of AP-1 composition from the ATF2:Jun to the Fos:Jun complex, with differentially invoked transcription cascades.