Nicole Rosskothen-Kuhl (Neurobiologisches Forschungslabor Universitäts-HNO-Klinik, Freiburg, Germany)

Abstract:
The adult brain has an impressive potential of neuroplasticity. Stimulating the central auditory system of rats with a cochlear implant (CI), we asked if changes in sensory input directly results in adult brain remodeling. Initially, we analyzed molecular short-term responses in hearing and deaf rats, characterizing the expression patterns of the molecular activity marker Fos after acute CI stimulation. We demonstrated that absence of hearing experience has far-reaching consequences for the interneuronal communication within networks of the adult auditory system. When hearing fails, CI stimulation entails expression of Fos in populations of neurons that are much larger than normally, essentially disregard tonotopic order, and lack much of spatio-temporal variations seen in hearing-experienced rats. Additionally, our experiments indicated that the Fos response in deaf, but not in hearing, rats was accompanied by a massive astrocytic hypertrophy. This suggests stimulation-induced remodeling processes within the central auditory system of deaf rats dependent on neuro-glia interaction.

In order to translate our initial results to realistic learning processes with lasting cellular changes taking place within days rather than hours, we stimulated hearing rats chronically for days. As a result we indicated a significant impact of input balance and activity pattern on the expression of plasticity-related genes in the adult brain. We identified the growth associated protein 43 (Gap43) as a marker useful for monitoring neurite outgrowth, synaptogenesis, and specific paths of synaptic activities. A failure in bilateral symmetry of auditory activation is directly reflected by Gap43 mRNA expression. Remarkably, this imbalance is prevented if a dysfunctional ear receives simple-patterned CI stimulation.

In summary, we have shown that synaptic cooperation may result in specific molecular modifications of neurons that are ready to be exploited for network re-organization. ...