Contribution of auditory nerve fibres to compound 1 action potential of the auditory nerve

23 Sound-evoked compound action potential (CAP), which captures the synchronous activation 24 of the auditory nerve fibres (ANFs), is commonly used to probe deafness in experimental and 25 clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low 26 sound-pressure levels activate the high-spontaneous rate (SR) fibres, and increasing levels 27 gradually recruit mediumand then low-SR fibres. Here, we quantitatively analyze the 28 contribution of the ANFs to CAP 6 days after 30 min-infusion of ouabain into the round 29 window niche. Anatomical examination showed a progressive ablation of ANFs, following 30 increasing concentration of ouabain. CAP amplitude and threshold plotted against ANFs loss 31 revealed 3 ANF pools: i) a highly ouabain-sensitive pool, which does not participate either in 32 the CAP threshold or in the amplitude, ii) a less sensitive pool, which only encoded CAP 33 amplitude, and iii) a resistant pool to ouabain, required for CAP threshold and amplitude. 34 Remarkably, the 3 pools distribution was similar to the SR-based ANF distribution (low-, 35 mediumand high-SR fibers), suggesting that the low-SR fibres loss leaves the CAP 36 unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis, and 37 further showed that it is due to their delayed and broad first spike latency distribution. In 38 addition to unraveling the neural mechanisms that encode CAP, our computational simulation 39 of an assembly of guinea pig ANFs, generalizes and extends our experimental findings to 40 different species of mammals. Altogether our data demonstrated that substantial auditory 41 nerve fibre loss can co-exist with normal hearing threshold, and even unchanged CAP 42 amplitude. 43