Regulation of mechanical input amplification in Drosophila hearing

Mechanical feedback amplification improves hearing. The strength of this feedback specifies the sensitivity of
the ear. Excess in this feedback, in turn, can lead to self-sustained oscillations, causing ringing in the ear. In
the interest of gaining insights into the molecular mechanisms ears employ to adjust their sensitivity to
external stimuli, we have started to genetically dissect the regulatory pathway that controls the gain of
mechanical amplification in the auditory system of the fly. Examination of the auditory mechanics in
Drosophila mutants revealed that the gain of amplification is negatively controlled via TRPVs: genetic
disruption of TRPV channel proteins causes excessive amplification and self-sustained oscillations. TRPVs
form calcium-permeable channels, suggesting that amplification is calcium-controlled. In effect, excess
amplification and self-sustained oscillations similar to those observed in TRPV mutants result from mutations
in calmodulin (Cam). Cam mutants are shown to display hypersensitive hearing, as judged from both the
receiver's mechanics and the electrical response in the antennal nerve. Our findings indicate that amplification
in Drosophila hearing is calcium-regulated, analogous to the calcium-dependent, transducer-based
amplificatory process known from many vertebrate ears. Whether genetic defects in TRPV channels and/or
calmodulin can cause ringing in vertebrate auditory systems remains to be seen.