Emergence of behavioral tinnitus in gerbils is associated with reduced spontaneous rates in single auditory nerve fibers

Tinnitus is often initiated by damage to the peripheral auditory system, for example by acoustic overexposure. Animal studies have shown that such noise-induced tinnitus is related to increased spontaneous activity in the dorsal cochlear nucleus as well as further along the central auditory pathway. However, the role of spontaneous activity of the auditory nerve, connecting the peripheral and central auditory systems, in tinnitus emergence remains unknown. In the current study, tinnitus was induced by exposing anesthetized Mongolian gerbils of either sex to a 115-dB SPL narrowband noise. After one day of recovery, animals were behaviorally tested for gap detection deficits using a gap-prepulse inhibition of the acoustic startle reflex (GPIAS) paradigm, indicative of tinnitus. Noise-induced threshold shifts did not differ between animals with and without signs of tinnitus. Interestingly, single auditory nerve fibers recorded from animals with signs of tinnitus had significantly reduced spontaneous rates compared to both noise-exposed animals without signs of tinnitus and sham-exposed animals. Furthermore, spontaneous rate reduction was specific to fibers tuned to frequencies within the frequency bands that showed gap detection deficits. On the other hand, inter-spike interval variability and bursting behavior increased in fibers from noise-exposed compared to sham-exposed animals but did not differ with gap detection deficits. These findings suggest that tinnitus-related central hyperactivity may be initiated by reduced spontaneous rates of its innervating auditory nerve fibers. This is consistent with theoretical models explaining the central manifestation of tinnitus and offers a more detailed definition of tinnitus-related deafferentation. Significance statement Decades of previous research showed that tinnitus strongly connects to peripheral cochlear damage and to neural aberrations in the central auditory system. However, up to now, the role of the auditory nerve, connecting the peripheral to the central auditory system, in the emergence of tinnitus pathology has remained unclear. The current study showed that spontaneous activity is significantly reduced in auditory nerve fibers recorded from noise-exposed animals with behavioral signs of tinnitus shortly after the exposure. This insight helps us to understand why certain central neural correlates of tinnitus emerge. Furthermore, understanding the physiological basis of the initiation phase of tinnitus may lead to new intervention strategies to treat it.