More than 10 million Americans suffer from noise induced hearing loss (NIHL). Short and long term noise exposure is a major hazard in certain """"""""normal"""""""" working and living environments. Noise exposure, depending on intensity and duration, can result in temporary or permanent auditory threshold shift (TTS, PTS). Recent studies have shown that synaptic efficacy deteriorates at the endbulb synapse in the anterior ventral cochlear nucleus (AVCN) in a strain of mice with age-related hearing loss. Furthermore, there is a functional reduction of entrainment to high frequency stimulation in postsynaptic bushy neurons. These changes are likely due to diminished activity in the afferent auditory nerve fibers. Noise insults, on the other hand, generate recurring short term hyperactivity in the auditory nerve. The excessive excitation could have detrimental effect on the endbulb synapse and its postsynaptic target. Because the AVCN provides vital cues to higher auditory centers for sound localization and speech recognition, it is essential to understand the functional consequences of noise induced hearing loss at this first relay synapse. Thus, we propose 2 specific aims. In the first aim, we will explicitly test the hypothesis that synaptic efficacy at the endbulb terminal is impaired immediately following noise exposure; however, the efficacy recovers with moderate insults resulting in only TTS, whereas the efficacy becomes permanently reduced in NIHL with PTS. We will take advantage of the low individual variability in noise exposure outcome in inbred CBA mice. Using a modified whole cochlear nucleus slice preparation, we will probe several aspects of synaptic transmission with electrophysiological recordings after noise overexposure. In the second aim, we will test the hypothesis that noise induced hearing loss affects the low threshold K+ conductance (lLT) in the postsynaptic bushy neurons; this effect in turn reduces the temporal coding capability in these neurons. We will characterize the lLT from bushy cells after inducing NIHL, and test the fine temporal coding of the bushy cell by activating the auditory nerve fiber with a realistic Poisson distributed spike train in the slice. Data from this project will complement and enhance the existing wealth of information regarding the peripheral effect of noise induced hearing loss. Ultimately we would like to address whether the integrity of the central auditory pathway can be preserved with drug or device intervention after NIHL, because CNS functional integrity is an essential component of successful post hearing loss intervention. ? ? ?
| Wang, Yong; Ren, Chongyu (2012) Effects of repeated ""benign"" noise exposures in young CBA mice: shedding light on age-related hearing loss. J Assoc Res Otolaryngol 13:505-15 |
| Wang, Yong; O'Donohue, Heather; Manis, Paul (2011) Short-term plasticity and auditory processing in the ventral cochlear nucleus of normal and hearing-impaired animals. Hear Res 279:131-9 |
| Wang, Yong; Ren, Chongyu; Manis, Paul B (2010) Endbulb synaptic depression within the range of presynaptic spontaneous firing and its impact on the firing reliability of cochlear nucleus bushy neurons. Hear Res 270:101-9 |
| Wang, Yong; Manis, Paul B (2008) Short-term synaptic depression and recovery at the mature mammalian endbulb of Held synapse in mice. J Neurophysiol 100:1255-64 |
| Wang, Yong; Manis, Paul B (2006) Temporal coding by cochlear nucleus bushy cells in DBA/2J mice with early onset hearing loss. J Assoc Res Otolaryngol 7:412-24 |
