Björn Nadrowski

Specification of auditory sensitivity by Drosophila TRP channels

Ears achieve their exquisite sensitivity by means of mechanical feedback: motile mechanosensory cells through their active motion boost the mechanical input from the ear. Examination of the auditory mechanics in Drosophila melanogaster mutants shows that the transient receptor potential (TRP) channel NompC is required to promote this feedback, whereas the TRP vanilloid (TRPV) channels Nan and Iav serve to control the feedback gain. The combined function of these channels specifies the sensitivity of the fly auditory organ.

Drosophila Auditory Organ Genes and Genetic Hearing Defects

The Drosophila auditory organ shares equivalent transduction mechanisms with vertebrate hair cells, and both are specified by atonal family genes. Using a whole-organ knockout strategy based on atonal, we have identified 274 Drosophila auditory organ genes. Only four of these genes had previously been associated with fly hearing, yet one in five of the genes that we identified has a human cognate that is implicated in hearing disorders. Mutant analysis of 42 genes shows that more than half of them contribute to auditory organ function, with phenotypes including hearing loss, auditory hypersusceptibility, and ringing ears. We not only discover ion channels and motors important for hearing, but also show that auditory stimulus processing involves chemoreceptor proteins as well as phototransducer components. Our findings demonstrate mechanosensory roles for ionotropic receptors and visual rhodopsins and indicate that different sensory modalities utilize common signaling cascades.

Mechanical Signatures of Transducer Gating in the Drosophila Ear

Hearing relies on dedicated mechanotransducer channels that convert sound-induced vibrations into electrical signals [1]. Linking this transduction to identified proteins has proven difficult because of the scarcity of native auditory transducers and their tight functional integration into ears [2-4]. We describe an in vivo paradigm for the noninvasive study of auditory transduction. By investigating displacement responses of the Drosophila sound receiver, we identify mechanical signatures that are consistent with a direct mechanotransducer gating in the flys ear. These signatures include a nonlinear compliance that correlates with electrical nerve responses, shifts with adaptation, and conforms to the gating-spring model of vertebrate auditory transduction. Analyzing this gating compliance in terms of the gating-spring model reveals striking parallels between the transducer mechanisms for hearing in vertebrates and flies. Our findings provide first insights into the mechanical workings of invertebrate mechanotransducer channels and set the stage for using Drosophila to specifically search for, and probe the roles of, auditory transducer components.

Transducer-Based Force Generation Explains Active Process in Drosophila Hearing

BACKGROUND Like vertebrate hair cells, Drosophila auditory neurons are endowed with an active, force-generating process that boosts the macroscopic performance of the ear. The underlying force generator may be the molecular apparatus for auditory transduction, which, in the fly as in vertebrates, seems to consist of force-gated channels that occur in series with adaptation motors and gating springs. This molecular arrangement explains the active properties of the sensory hair bundles of inner-ear hair cells, but whether it suffices to explain the active macroscopic performance of auditory systems is unclear. RESULTS To relate transducer dynamics and auditory-system behavior, we have devised a simple model of the Drosophila hearing organ that consists only of transduction modules and a harmonic oscillator that represents the sound receiver. In vivo measurements show that this model explains the ears active performance, quantitatively capturing displacement responses of the flys antennal sound receiver to force steps, this receivers free fluctuations, its response to sinusoidal stimuli, nonlinearity, and activity and cycle-by-cycle amplification, and properties of electrical compound responses in the afferent nerve. CONCLUSIONS Our findings show that the interplay between transduction channels and adaptation motors accounts for the entire macroscopic phenomenology of the active process in the Drosophila auditory system, extending transducer-based amplification from hair cells to fly ears and demonstrating that forces generated by transduction modules can suffice to explain active processes in ears.

Direct gating and mechanical integrity of Drosophila auditory transducers require TRPN1

The elusive transduction channels for hearing are directly gated mechanically by the pull of gating springs. We found that the transient receptor potential (TRP) channel TRPN1 (NOMPC) is essential for this direct gating of Drosophila auditory transduction channels and that the channel-spring complex was disrupted if TRPN1 was lost. Our results identify TRPN1 as a mechanical constituent of the flys auditory transduction complex that may act as the channel and/or gating spring.

Antennal hearing in insects – New findings, new questions

Mosquitoes, certain Drosophila species, and honey bees use Johnstons organ in their antennae to detect the wing-beat sounds of conspecifics. Recent studies on these insects have provided novel insights into the intricacies of insect hearing and sound communication, with main discoveries including transduction and amplification mechanisms as known from vertebrate hearing, functional and molecular diversifications of mechanosensory cells, and complex mating duets that challenge the frequency-limits of insect antennal ears. This review discusses these recent advances and outlines potential avenues for future research.

Level-dependent auditory tuning Transducer-based active processes in hearing and best-frequency shifts

Ears boost their sensitivity by means of active, force-generating processes to augment the minute vibrations induced by soft sounds. These processes can alter auditory frequency–tuning in a level-dependent way. In the antennal hearing organ of Drosophila, for example, the active process shifts the best-frequency (BF) of the antennal sound receiver when the sound intensity is varied, tuning the receiver to conspecific songs. Here we show that this level-dependent tuning can be reproduced by an active transduction model as proposed for vertebrate hair cells and the Drosophila ear. We further show that the direction of the frequency shift depends on the system to which the molecular modules for auditory transduction connect: If this system is mass-less such as the sensory hair bundles of bullfrog saccular hair cells, the BF of the displacement response will increase as the sound intensity declines. Conversely, BF will decrease with declining intensity if the transduction modules couple to inertial systems such as the fly’s antennal sound receiver or cupulae in the fish lateral line.

Using Drosophila for studying fundamental processes in hearing.

Apart from detecting sounds, vertebrate ears occasionally produce sounds. These spontaneous otoacoustic emissions are the most compelling evidence for the existence of the cochlear amplifier, an active force-generating process within the cochlea that resides in the motility of the hair cells. Insects have neither a cochlea nor hair cells, yet recent studies demonstrate that an active process that is equivalent to the cochlear amplifier occurs in at least some insect ears; like hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila actively generate forces that augment the minute vibrations they transduce. This neuron-based force-generation, its impact on the ears macroscopic performance, and the underlying molecular mechanism are the topics of this article, which summarizes some of the recent findings on how the Drosophila organ of hearing works. Functional parallels with vertebrate auditory systems are described that recommend the fly for the study of fundamental processes in hearing.

Drosophila mechanotransduction - Linking proteins and functions

The sensation of touch, gravity, and sound all rely on dedicated ion channels that transduce mechanical stimulus forces into electrical response signals. The functional workings and molecular identities of these mechanotransducer channels are little understood. Recent work shows that the mechanotransducers for fly and vertebrate hearing share equivalent gating mechanisms, whereby this mechanism can be probed non-invasively in the mechanics of the Drosophila ear. Here, we describe how this mechanics can be used to evaluate the roles of identified proteins in the process of mechanosensation and, specifically, their contributions to mechanotransduction.

Modeling auditory transducer dynamics.

Purpose of reviewThis article reviews the literature on the modeling of auditory transducer dynamics. Theoretical descriptions and computational models of transducer dynamics are presented and discussed. Recent findingsSince the introduction of the gating-spring model of hair cell mechanotransduction in 1983, theories of auditory transducer dynamics have been developed along with the accumulation of electrophysiological and mechanical data. Recent findings suggest that the auditory transduction apparatus might be very similar across vertebrates and invertebrates, and that auditory transducer dynamics can shape the performance of entire hearing organs. SummaryThe sense of hearing relies on a small number of transduction modules that convert minute mechanical stimuli into electrical signals. Models have been proposed that describe how this transduction works. These models may help to understand the biophysics of mechanoelectrical signal transduction, the contribution of transducer dynamics to auditory signal processing, and to link transducer function and genes.