Modulation of P-CREB and expression of c-Fos in cochlear nucleus and superior olive following electrical intracochlear stimulation

Abstract

Investigating activity-dependent plasticity in the auditory brain stem of the adult rat, we observed that electrical intracochlear stimulation led to a tonotopically localized modulation of the phosphorylation of the cAMP response element binding protein (CREB) and an equally localized expression of the immediate early gene product c-Fos in cochlear nucleus and superior olive. As P-CREB is thought to act as transcription factor on one promoter site of the c-fos gene, we compared immunolabeling for P-CREB and c-fos in adjacent brain sections. Following 2h sustained stimulation in previously deafened animals, labelling for P-CREB declined in regions where c-Fos labelling increased. This suggests that the level or state of P-CREB (e.g. whether it is phosphorylated or not) are affected by intracochlear stimulation in a process that appears to be linked to the stimulation-dependent expression of c-Fos in auditory brain stem nuclei.

The Cochlear Implant in Action: Molecular Changes Induced in the Rat Central Auditory System

“…Others reported distinctly different patterns of c-Fos expression upon EIS (Illing & Michler, 2001;Saint Marie et al, 1999A, 1999B;Saito et al, 1999;Zhang et al, 1998). In several studies involving electrical stimulation, tonotopic patterns of c-Fos expression were found (Saito et al, 1999;Nagase et al, 2000;Saito et al, 2000;Illing & Michler, 2001), but others did not report it (Nakamura et al, 2005). c-Fos has also been induced after neonatal auditory deprivation (Keilmann & Herdegen, 1995; and in kanamycin-deafened rats (Fujii et al, 1997;Nagase et al, 2003).…”

“…CREB phosphorylation is modulated in cochlear nucleus and superior olivary complex as a consequence of electrical stimulation in the cochlea (Illing & Michler, 2001). Apart from CRE, the c-fos promoter contains a sis inducible element (SIE), a serum response element (SRE), and an activator protein-1 (AP-1)-like sequence (FAP) (Herdegen & Leah, 1998.).…”

“…Electrical intracochlear stimulation (EIS) as done with CIs in humans was shown to be similarly effective as acoustical stimulation in driving cells to express c-Fos (Roullier et al, 1992;Illing & Michler, 2001;Nakamura et al, 2003). Subsequent studies showed a marked variability in the pattern of stimulation-dependent c-Fos expression in the auditory brainstem.…”

“…Some studies reported massive induction of c-Fos in dorsal cochlear nucleus (DCN), with little expression in ventral cochlear nucleus (VCN), and a substantial increase of c-Fos immunoreactivity in the external nuclei of the inferior colliculus (IC), with little staining in its central nucleus CIC (Vischer et al, 1994;1995;Zhang et al, 1996). Others reported distinctly different patterns of c-Fos expression upon EIS (Illing & Michler, 2001;Saint Marie et al, 1999A, 1999B;Saito et al, 1999;Zhang et al, 1998). In several studies involving electrical stimulation, tonotopic patterns of c-Fos expression were found (Saito et al, 1999;Nagase et al, 2000;Saito et al, 2000;Illing & Michler, 2001), but others did not report it (Nakamura et al, 2005).…”

“…The Cochlear Implant in Action: Molecular Changes Induced in the Rat Central Auditory System 145 immunocytochemistry based on diaminobenzidine staining or immunfluorescence (cp. Illing & Michler, 2001;Rosskothen et al, 2008;.…”