Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice

Abstract

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after agerelated high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed nonlinear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.

Age-related changes in GAD levels in the central auditory system of the rat

“…A similar situation exists in another species, in mice: hearing function in the CBA/CaJ strain of mice deteriorates very slowly as in the Long-Evans strain of rats, whereas the C57BL/6J strain is known to undergo rapid deterioration with early deafness (Parham, 1997, Spongr et al, 1997. In spite of these differences in age-related defects of auditory function, which are mostly caused by pathologies in the inner ear, significant age-related alterations of the inhibitory function in the central auditory system were reported in both strains of mice (Walton et al, 1998(Walton et al, , 2002Felix and Portfors, 2007). Therefore, we may tentatively suggest that the age-related decline in GAD expression in the IC and AC demonstrated in our experiments does not depend primarily on peripheral deafferentation but is, at least partially, of central origin.…”

Sensitive Response to Low-Frequency Cochlear Distortion Products in the Auditory Midbrain

“…3). This behavior could be produced by facilitatory mechanisms in the IC as they are reported for bats (e.g., Portfors and Wenstrup 2002) and rodents (Egorova et al 2001;Felix and Portfors 2007). In a study on mice, Portfors and Felix (2005) could demonstrate that 16% of the neurons had a response rate increase of Ն20% during presentation of an additional high-frequency tone.…”

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice

“…Multiple tuned and combination-sensitive neurons are found in the IC of both mustached bats [26] and mice [27]. Felix and Portfors (2007) found that the majority of combination-sensitive and multiple tuned neurons are sensitive to high frequencies which led them to suggest that response properties of these types of neurons will be affected by age-related high frequency hearing loss. They further hypothesized that high frequency hearing loss reduces spectral integration properties in the IC.…”

“…Within the central auditory system the IC, the principal midbrain nucleus of the auditory pathway, has been described to undergo morphological and functional changes underlying age-related hearing loss [13,14]. To identify potential target genes for Tff3 in the IC we used a microarray-based screen.…”

“…By studying ABR responses we investigated if the auditory processing pathway is obstructed in Tff3 knock-out animals, whereas examination of different cochlear protein markers may reveal if lack of Tff3 affects expression of particular genes in the cochlea. Lack of striking differences in the cochlea using these assays together with interesting data about functional changes underlying age-related hearing loss in the inferior colliculus (IC) [13,14] turned our attention to the auditory central nervous system (CNS). We thus performed a microarray-based expression screening of genes differentially expressed in the IC followed by confirmation using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).…”