Nelson's notch in the rate-level functions of auditory-nerve fibers might be caused by PIEZO2-mediated reverse-polarity currents in hair cells

Abstract

Half a century ago, Nelson Kiang and colleagues observed that some spike rate versus stimulus level functions of auditory-nerve-fiber responses to tones are nonmonotonic, exhibiting a sharp notch (“Nelson's notch”) at high stimulus levels. The notch is associated with an abrupt change in the phase of the response by ∼180°. To account for these findings, Kiang proposed a “two-factor cancellation hypothesis” according to which excitation of an auditory-nerve fiber is produced by the sum of two phase-locked factors with opposite phase and with different dependencies on stimulus level, cancelling each other at stimulus levels within the notch. The first factor, which dominates at lower stimulus levels, is likely based on the mechanoelectrical transducer current through mechanoelectrical transducer channels in the tips of the inner-hair-cell stereocilia. The identity of the second factor, which dominates at high stimulus levels, has remained elusive. Here, we hypothesize that the second factor is based on the “anomalous” or “reverse-polarity” currents entering inner hair cells via a second type of mechanosensitive channel, PIEZO2, recently identified in the apical surface of hair cells rather than the tips of their stereocilia.