Loss of auditory sensitivity from inner hair cell synaptopathy can be centrally compensated in the young but not old brain

Abstract

A dramatic shift in societal demographics will lead to rapid growth in the number of older people with hearing deficits. Poorer performance in suprathreshold speech understanding and temporal processing with age has been previously linked with progressing inner hair cell (IHC) synaptopathy that precedes age-dependent elevation of auditory thresholds. We compared central sound responsiveness after acoustic trauma in young, middle-aged, and older rats. We demonstrate that IHC synaptopathy progresses from middle age onward and hearing threshold becomes elevated from old age onward. Interestingly, middle-aged animals could centrally compensate for the loss of auditory fiber activity through an increase in late auditory brainstem responses (late auditory brainstem response wave) linked to shortening of central response latencies. In contrast, old animals failed to restore central responsiveness, which correlated with reduced temporal resolution in responding to amplitude changes. These findings may suggest that cochlear IHC synaptopathy with age does not necessarily induce temporal auditory coding deficits, as long as the capacity to generate neuronal gain maintains normal sound-induced central amplitudes.

Age-related changes in envelope-following responses at equalized peripheral or central activation

“…Peripheral activation in the present study was measured using ABR wave I, which is proportional to the number of intact IHC-AN synapses [Chambers et al, 2016, Möhrle et al, 2016, Sergeyenko et al, 2013]. Comparable wave I amplitudes therefore suggest comparable aggregate numbers of IHC-AN synapses synchronously and transiently activated by the tone ABR stimuli used.…”

“…Comparable wave I amplitudes therefore suggest comparable aggregate numbers of IHC-AN synapses synchronously and transiently activated by the tone ABR stimuli used. Although IHC-AN synapses are not required for some degrees of sound detection and discrimination [Chambers et al, 2016, Wang et al, 1997], their function is correlated with rapid temporal processing [Chambers et al, 2016, Möhrle et al, 2016]. The present study used supra-threshold sound levels (40–50 dB SL) that would drive activation of high and low spontaneous rate auditory nerve fibers.…”

Biomarkers for Hearing Dysfunction: Facts and Outlook

“…In conclusion, an increasing number of studies have now demonstrated that the counting of IHC ribbons after hearing loss, for example, in aged specimens [62,64] , or after an acoustic trauma [22,31,32,61,75,76] , or after intake of aminoglycoside [77,78] , can be a first indication of the loss of IHC synapses and AN integrity, independent of (elevated) hearing thresholds.…”

“…Low sound pressure levels first activate the high-SR fibers, meaning that intact CAP thresholds can provide an estimate about intact high-SR fibers. On the flip side, increasing sound pressure in a row drives the medium-and low-SR fibers, the latter being the most vulnerable to noise [61][62][63][64][65] but which do not contribute to CAP responses at threshold [66] .…”

“…2 ). In humans, the absolute latencies and supra-threshold amplitudes of waves, ABR wave I (distal peripheral portion of the AN [90] ), ABR wave III (fibers from cochlear nucleus to caudal auditory pons and superior olivary complex [91] ), ABR wave VI (medial geniculate body or the auditory thalamus), or ARB wave V (believed to correspond with the IC in the midbrain [92,93] ) can be analyzed for various stimulus intensity levels and, for example, recording time of ABR measurements that should be set at >10 ms. An increasing body of evidence demonstrates that, due to altered leisure behavior and demographic crisis, the hidden hearing loss and auditory neuropathy are likely widely prevalent over time [94][95][96] , contributing to presbycusis [62,64,97] or hyperacusis and tinnitus [21,22,98] .…”