Dataset Information

Expression of amyloid-? in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception.

ABSTRACT: Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-? (A?), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the A?-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor A?-induced neuronal dysfunction quantitatively over time.

SUBMITTER: Omata Y

PROVIDER: S-EPMC4833138 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression of amyloid-β in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception.

Omata Yasuhiro Y Tharasegaran Suganya S Lim Young-Mi YM Yamasaki Yasutoyo Y Ishigaki Yasuhito Y Tatsuno Takanori T Maruyama Mitsuo M Tsuda Leo L

Aging 20160301 3

Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that ...[more]

PMID: 26959388

Similar Datasets

Project description:Spatial hearing skills are essential for children as they grow, learn and play. These skills provide critical cues for determining the locations of sources in the environment, and enable segregation of important sounds, such as speech, from background maskers or interferers. Spatial hearing depends on availability of monaural cues and binaural cues. The latter result from integration of inputs arriving at the two ears from sounds that vary in location. The binaural system has exquisite mechanisms for capturing differences between the ears in both time of arrival and intensity. The major cues that are thus referred to as being vital for binaural hearing are: interaural differences in time (ITDs) and interaural differences in levels (ILDs). In children with normal hearing (NH), spatial hearing abilities are fairly well developed by age 4-5 years. In contrast, most children who are deaf and hear through cochlear implants (CIs) do not have an opportunity to experience normal, binaural acoustic hearing early in life. These children may function by having to utilize auditory cues that are degraded with regard to numerous stimulus features. In recent years there has been a notable increase in the number of children receiving bilateral CIs, and evidence suggests that while having two CIs helps them function better than when listening through a single CI, these children generally perform worse than their NH peers. This paper reviews some of the recent work on bilaterally implanted children. The focus is on measures of spatial hearing, including sound localization, release from masking for speech understanding in noise and binaural sensitivity using research processors. Data from behavioral and electrophysiological studies are included, with a focus on the recent work of the authors and their collaborators. The effects of auditory plasticity and deprivation on the emergence of binaural and spatial hearing are discussed along with evidence for reorganized processing from both behavioral and electrophysiological studies. The consequences of both unilateral and bilateral auditory deprivation during development suggest that the relevant set of issues is highly complex with regard to successes and the limitations experienced by children receiving bilateral cochlear implants. This article is part of a Special Issue entitled <Annual Reviews 2016>.

Project description:Previous studies on the effect of spectral content on auditory distance perception (ADP) focused on the physically measurable cues occurring either in the near field (low-pass filtering due to head diffraction) or when the sound travels distances >15 m (high-frequency energy losses due to air absorption). Here, we study how the spectrum of a sound arriving from a source located in a reverberant room at intermediate distances (1-6 m) influences the perception of the distance to the source. First, we conducted an ADP experiment using pure tones (the simplest possible spectrum) of frequencies 0.5, 1, 2, and 4 kHz. Then, we performed a second ADP experiment with stimuli consisting of continuous broadband and bandpass-filtered (with center frequencies of 0.5, 1.5, and 4 kHz and bandwidths of 1/12, 1/3, and 1.5 octave) pink-noise clips. Our results showed an effect of the stimulus frequency on the perceived distance both for pure tones and filtered noise bands: ADP was less accurate for stimuli containing energy only in the low-frequency range. Analysis of the frequency response of the room showed that the low accuracy observed for low-frequency stimuli can be explained by the presence of sparse modal resonances in the low-frequency region of the spectrum, which induced a non-monotonic relationship between binaural intensity and source distance. The results obtained in the second experiment suggest that ADP can also be affected by stimulus bandwidth but in a less straightforward way (i.e., depending on the center frequency, increasing stimulus bandwidth could have different effects). Finally, the analysis of the acoustical cues suggests that listeners judged source distance using mainly changes in the overall intensity of the auditory stimulus with distance rather than the direct-to-reverberant energy ratio, even for low-frequency noise bands (which typically induce high amount of reverberation). The results obtained in this study show that, depending on the spectrum of the auditory stimulus, reverberation can degrade ADP rather than improve it.

Project description:BackgroundOuter hair cells are the specialized sensory cells that empower the mammalian hearing organ, the cochlea, with its remarkable sensitivity and frequency selectivity. Sound-evoked receptor potentials in outer hair cells are shaped by both voltage-gated K(+) channels that control the membrane potential and also ligand-gated K(+) channels involved in the cholinergic efferent modulation of the membrane potential. The objectives of this study were to investigate the tonotopic contribution of BK channels to voltage- and ligand-gated currents in mature outer hair cells from the rat cochlea.Methodology/principalFindings In this work we used patch clamp electrophysiology and immunofluorescence in tonotopically defined segments of the rat cochlea to determine the contribution of BK channels to voltage- and ligand-gated currents in outer hair cells. Although voltage and ligand-gated currents have been investigated previously in hair cells from the rat cochlea, little is known about their tonotopic distribution or potential contribution to efferent inhibition. We found that apical (low frequency) outer hair cells had no BK channel immunoreactivity and little or no BK current. In marked contrast, basal (high frequency) outer hair cells had abundant BK channel immunoreactivity and BK currents contributed significantly to both voltage-gated and ACh-evoked K(+) currents.Conclusions/significanceOur findings suggest that basal (high frequency) outer hair cells may employ an alternative mechanism of efferent inhibition mediated by BK channels instead of SK2 channels. Thus, efferent synapses may use different mechanisms of action both developmentally and tonotopically to support high frequency audition. High frequency audition has required various functional specializations of the mammalian cochlea, and as shown in our work, may include the utilization of BK channels at efferent synapses. This mechanism of efferent inhibition may be related to the unique acetylcholine receptors that have evolved in mammalian hair cells compared to those of other vertebrates.

Dataset Information

Expression of amyloid-? in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception.

Publications

Expression of amyloid-β in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets