Noise-Induced Synaptic Loss and Vestibular Dysfunction

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Abstract Vestibular dysfunction is a significant public health problem. Agrawal et al. (2009) reported that 35% of adults older than 40 had evidence of postural instability. Balance dysfunction is linked to an increased likelihood of falling and in the U.S. falls are responsible for more than 50% of accidental deaths. Although the causes of vestibular dysfunction are multiple, recent studies suggest a linkage between noise-induced hearing loss and vestibular dysfunction (Akin et al. 2012; Golz et al. 2001; Guest et al. 2011; Zuniga et al 2012). The suggestion that noise exposure is also a risk factor for vestibular dysfunction is controversial as there is only limited experimental support for causal relationships between noise exposure and peripheral vestibular pathology and behavioral symptoms (e.g., poor balance). In our recently published study (Stewart et al. 2018), we exposed rats to 6 hours of 120dB SPL low frequency noise (3-octave band centered at 1500Hz) and found that neural activity in the vestibular nerve was reduced, as assessed by the vestibular short latency evoked potential (VsEP). Noise exposed animals also exhibited reduced numbers of immunostained afferents with calyx endings, especially calyx-only afferents that terminate on hair cells located in the striolar region of the sacculus (Stewart et al. 2018). More recent experiments show that noise, depending on its intensity, can cause either temporary or permanent threshold shifts of VsEP responses to jerk stimuli. Permanent noise induced VsEP threshold shifts could reflect loss of calyces and/or concomitant loss of ribbon synapses within calyces. This loss might be permanent or there could be recovery associated with reconnection of calyces or recovery of synapses. We hypothesize that noise disrupts peripheral vestibular synapses and/or synaptic transmission, transiently or permanently and causes functional vestibular loss. Determining the basis for synaptic/signal transmission failure in the vestibular periphery and the parameters that characterize damaging noise is a critical first step toward development of future preventative measures. Specific Aim 1 will determine the parameters of noise that causes temporary versus permanent changes to the VsEP and to peripheral vestibular nerve terminals and their synapses in the saccular and utricular maculae. Specific Aim 2 will extend the analysis of Aim 1 to examine the semicircular canal cristae and compare noise-induced changes in the cristae with those observed in the otolith organs. Specific Aim 3 will correlate changes in VsEP responses and noise induced synaptic pathology with behavioral assays: a beam crossing task, an otolith dependent behavior (macular ocular reflex, MOR), and a semicircular canal dependent behavior (vestibuloocular reflex, VOR).