title: Fos-like immunoreactivity in the auditory brainstem evoked by bipolar intracochlear electrical stimulation: effects of current level and pulse duration.
abstract: Fos-like immunoreactivity was used to compare the auditory brain stem excitation elicited by bipolar electrical stimulation of the cochlea at various current levels relative to the electrically evoked auditory brain stem response threshold for a 50-micros/phase monophasic pulse. Fos-like immunoreactive cells were labeled in primary auditory brain stem regions. The distribution of labeled cells was restricted to regions known to be cochleotopically related to the stimulated region of the scala tympani. Some labeled cells were observed at 2x electrically evoked auditory brain stem response threshold. The number, density and spatial distribution of labeled cells were quantified in the dorsal cochlear nucleus and inferior colliculus, and found to increase with increasing level of stimulation. For 50-micros pulses, the location of labeled neurons remained reasonably restricted to narrow bands within each region until the 1Ox level of stimulation (20 dB above electrically evoked auditory brain stem response threshold) was reached. While a monotonic increase in Fos-like immunoreactivity with increasing stimulus level was observed in most nuclei, for cells of the superficial layer of the dorsal cochlear nucleus, a non-monotonic change with increasing stimulus level was seen. This dorsal cochlear nucleus non-monotonicity may indicate that, at higher levels of stimulation, a secondary indirect inhibitory input, probably associated with activation of deep layer dorsal cochlear nucleus cells, reduces excitatory responses at the superficial layer of the dorsal cochlear nucleus. Electrically evoked auditory brain stem response and Fos expression showed parallel changes as a function of stimulus level and pulse duration. The data indicate that discrete activation of cell populations within the central auditory pathways can occur with bipolar electrical stimulation to the highest levels of stimulation typically useful in humans. The data also indicate a close, but not identical, quantitative relationship between Fos-like immunoreactivity and electrophysiological response amplitude. These findings support the view that a study of Fos-like immunoreactivity can provide a powerful and quantitative tool for study of the dynamic response characteristics of cells of the central auditory system to electrical stimulation at suprathreshold levels. The data suggest that there is a monotonic increase in the number of neurons responsive to intracochlear electrical stimulation as a function of stimulus level, at least through the upper half of the dynamic range, but that this increase does not result in a complete loss of spatial selectivity. Coupled with previous psychophysical studies, these results suggest that the increase in the number of activated neurons is functionally beneficial, resulting in improved discrimination of changes in the electrical signals.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical Center, Ann Arbor 48109-0506, USA.
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: J M
authors.initials: JM
authors.lastname: Miller
authors.forename: B E
authors.initials: BE
authors.lastname: Pfingst
authors.forename: R A
authors.initials: RA
authors.lastname: Altschuler
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000166:cytology / Q000502:physiology; D001309:Auditory Threshold / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism / Q000502:physiology*; D003051:Cochlea / Q000502:physiology*; D017626:Cochlear Nucleus / Q000378:metabolism / Q000502:physiology; D004558:Electric Stimulation; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013477:Superior Colliculi / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
chemical_list: D016760:Proto-Oncogene Proteins c-fos