Physiological, anatomical, and behavioral changes after acoustic trauma in Drosophila melanogaster

Abstract

Noise-induced hearing loss (NIHL) is a growing health issue, with costly treatment and lost quality of life. Here we establish Drosophila melanogaster as an inexpensive, flexible, and powerful genetic model system for NIHL. We exposed flies to acoustic trauma and quantified physiological and anatomical effects. Trauma significantly reduced sound-evoked potential (SEP) amplitudes and increased SEP latencies in control genotypes. SEP amplitude but not latency effects recovered after 7 d. Although trauma produced no gross morphological changes in the auditory organ (Johnston's organ), mitochondrial cross-sectional area was reduced 7 d after exposure. In nervana 3 heterozygous flies, which slightly compromise ion homeostasis, trauma had exaggerated effects on SEP amplitude and mitochondrial morphology, suggesting a key role for ion homeostasis in resistance to acoustic trauma. Thus, Drosophila exhibit acoustic trauma effects resembling those found in vertebrates, including inducing metabolic stress in sensory cells. This report of noise trauma in Drosophila is a foundation for studying molecular and genetic sequelae of NIHL. mitochondria | Na/K ATPase | locomotion | auditory courtship behavior N oise-induced hearing loss (NIHL) is a pervasive and growing health issue arising from occupational and recreational hazards, with significant costs in health care and personal quality of life. Despite this, the molecular and physiological mechanisms involved in the etiology or recovery from injury are not yet fully understood. Importantly, intense acoustic trauma can induce permanent damage-unlike other vertebrates, mammals cannot regenerate auditory hair cells (1, 2). NIHL associated with permanent changes in auditory sensitivity causes multiple consistent effects: stereocilia bundle disruption, inner (IHC) and outer hair cell (OHC) death or damage, supporting cell tissue disruption, and eventual spiral ganglion cell damage or loss (3-7). Most studies to date used mammalian model organisms such as mice (8, 9), rats (10), and guinea pigs (11)(12)(13)(14). These animals have difficult access to the inner ear inside the temporal bone and high maintenance costs coupled with relatively long generation times.Drosophila is a compelling alternative model system with strong genetic tools, inexpensive production of large numbers of animals, and an accessible auditory system that is becoming better understood genetically and physiologically. During courtship, Drosophila males vibrate their wings to produce a courtship song composed of pulse and sinusoidal components (15,16). This song facilitates species identification and mate selection (16,17). Drosophila males and females detect airborne vibrations via Johnston's organ (JO) in the second antennal segment (18). The JO is an array of chordotonal mechanoreceptors (or scolopidia; Fig. 1 A-C). Via the aristae, acoustic energy is transformed to rotational movement of the third antennal segment, activating mechanosensitive channels on JO neuron dendrites. Like vertebrate hair cells, JO ne...

Frequency of the Audiometric Notch Following Excessive Noise Exposure

“…Exposure to very loud sounds can produce a permanent hearing loss by irreplaceably damaging the sensory cells (hair cells) and auditory neurons in the cochlea (Peppi et al, 2011). The molecular and physiological mechanisms involved in the etiology or recovery from injury are not yet fully understood (Christie et al, 2013). Overexposure to noise has been known to cause the occupational hearing loss.…”

Noise-induced hearing loss

“…While morphologically divergent from the hair cell format, chordotonal organs share developmental genetic pathways with vertebrate auditory hair cells, including specification and differentiation transcription factors Pax2, Atoh1, spalt and others (reviewed recently by [39]). Drosophila hearing, which is used to detect species-specific courtship sounds produced by male wing vibration, has been shown to display high temporal resolution of auditory stimuli [40], frequency tuning [41], rapid adaptation [40, 42], wide dynamic range facilitated by nonlinear amplification mechanisms [43], active mechanisms in mechanoreceptive structures [43-45], and most recently, responses to noise trauma [46]. …”

“…To understand how research in Drosophila hearing mechanisms could illuminate the molecular pathways underlying noise-induced hearing loss, we began to study the responses of flies exposed to loud noise [46]. To achieve the goal of maximal duty cycle stimulation in the antenna, which is not tonotopically organized, we elected to use a pure tone trauma stimulus of 250 Hz which approximates the antenna's best frequency [46].…”

“…To achieve the goal of maximal duty cycle stimulation in the antenna, which is not tonotopically organized, we elected to use a pure tone trauma stimulus of 250 Hz which approximates the antenna's best frequency [46]. Flies subjected to this tone at 120 dB for 24 hr showed significantly reduced hearing immediately after the trauma, as measured by extracellular potentials in the antennal nerve, which carries the axons of the sensory neurons.…”

“…These sound-evoked potentials (SEPs) are roughly equivalent to compound action potentials recorded from the mammalian auditory nerve. The SEP amplitudes were reduced up to 50% immediately after trauma, relative to untraumatized controls, with partial recovery after 1 day and full recovery by 7 days post-trauma [46]. Remarkably, the sensory neurons did not die, as would mammalian hair cells subjected to similar levels of noise trauma.…”