Transcription factor modulation and expression in the rat auditory brainstem following electrical intracochlear stimulation.
Neuronal activity in sensory organs elicited by adequate or electrical stimulation not only invokes fast electrical responses but may also trigger complex molecular changes inside central neurons. Following electrical intracochlear stimulation with a cochlear implant under urethane anesthesia, we observed changes in the phosphorylation state of the cAMP response element binding protein (CREB) and the expression of the immediate-early genes c-fos and egr-1, molecules known to act as transcription factors, in a tonotopically precise pattern in central auditory neurons. These neurons resided in the posteroventral and anteroventral cochlear nucleus, the dorsal cochlear nucleus, the lateral superior olive, the medial nucleus of the trapezoid body, the dorsal and ventral nucleus of the lateral lemniscus, and the central nucleus of the inferior colliculus. Moreover, effects of electrical stimulation were identified in the medial vestibular nucleus and the lateral parabrachial nucleus. Regionally, CREB was dephosphorylated wherever immediate-early gene expression went up. These massive stimulation-dependent modulations of transcription factors in the ascending auditory system are indicative of ongoing changes that modify the chemistry and structure of the affected cells and, consequently, their response characteristics to subsequent stimulation of the inner ear.
Illing
Robert-Benjamin
RB
Neurobiological Research Laboratory, Department of Otorhinolaryngology, University of Freiburg, Killianstrasse 5, Freiburg, D-79106, Germany. rbi@ukl.uni-freiburg.de
Michler
Steffen A
SA
Kraus
K Suzanne
KS
Laszig
Roland
R
D000818:Animals; D001306:Auditory Pathways / Q000033:anatomy & histology / Q000378:metabolism*; D001309:Auditory Threshold; D001710:Biotin / Q000031:analogs & derivatives*; D001933:Brain Stem / Q000033:anatomy & histology / Q000378:metabolism*; D003051:Cochlea / Q000502:physiology* / Q000601:surgery; D003054:Cochlear Implants; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003911:Dextrans; D051766:Early Growth Response Protein 1; D004558:Electric Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D005260:Female; D017874:Immediate-Early Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D003911:Dextrans; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; C076397:biotinylated dextran amine; D001710:Biotin