On the value of diverse organisms in auditory research: From fish to flies to humans

Abstract

Historically, diverse organisms have contributed to our understanding of auditory function. In recent years, the laboratory mouse has become the prevailing non-human model in auditory research, particularly for biomedical studies. There are many questions in auditory research for which the mouse is the most appropriate (or the only) model system available. But mice cannot provide answers for all auditory problems of basic and applied importance, nor can any single model system provide a synthetic understanding of the diverse solutions that have evolved to facilitate effective detection and use of acoustic information. In this review, spurred by trends in funding and publishing and inspired by parallel observations in other domains of neuroscience, we highlight a few examples of the profound impact and lasting benefits of comparative and basic organismal research in the auditory system. We begin with the serendipitous discovery of hair cell regeneration in non-mammalian vertebrates, a finding that has fueled an ongoing search for pathways to hearing restoration in humans. We then turn to the problem of sound source localization - a fundamental task that most auditory systems have been compelled to solve despite large variation in the magnitudes and kinds of spatial acoustic cues available, begetting varied direction-detecting mechanisms. Finally, we consider the power of work in highly specialized organisms to reveal exceptional solutions to sensory problems - and the diverse returns of deep neuroethological inquiry - via the example of echolocating bats. Throughout, we consider how discoveries made possible by comparative and curiosity-driven organismal research have driven fundamental scientific, biomedical, and technological advances in the auditory field.

Keywords: Comparative auditory neuroscience; Echolocation; Hair cell regeneration; Neuroethology; Sound source localization.

Fig. 1.. Trends in funding and publishing across nonhuman auditory systems over the past 20 years.

A. Number of auditory publications over the past 20 years retrieved from PubMed using primary search term “hearing” and secondary search term <taxa as indicated>. The grouped term Non-primate mammals included the following terms: bat, rabbit, chinchilla, gerbil, guinea pig, ferret, hamster, feline, pig, elephant. Black box demarcates data expanded in panel B. B. Inset from panel A with expanded y-axis to enable visualization of included traces; secondary search terms, or groups of terms, as labeled. Groups of terms were composed as follows: Fish – fish, zebrafish; Birds – avian, owl, chick, songbird; Insects – drosophila, insect; Amphibians and reptiles – amphibian, frog, reptile, lizard; Non-human primates – non-human primate, macaque (monkey was not included in the grouped term “non-human primates” due to a high number of irrelevant results). C. Grants funded by NIH over the past 20 years retrieved from NIH RePORTER using primary search term “hearing” and secondary search term <taxa as indicated>. Black box demarcates data expanded in panel D. D. Inset from panel C; secondary search terms, or groups of terms, as labeled. Groups of terms were composed as follows: Non-primate mammals – bat, rabbit, chinchilla, gerbil, guinea pig, ferret, hamster, feline, pig, elephant; Birds – avian, owl, chick, songbird; Non-human primate – non-human primate, monkey, macaque; Fish – fish, zebrafish; Insects – drosophila, insect; Amphibians and reptiles – amphibian, frog, reptile, lizard.

Fig. 2.. Hair cell regeneration in vertebrates.

Despite divergent evolution including wide structural variation in inner ear /hair-cell-bearing end organs, all studied non-mammalian vertebrates demonstrate the capacity for robust hair cell regeneration. Three representative species are shown (bottom row) possessing varied inner ear structures (middle row), but conserved mechanisms for regeneration (top row; adaptation of schematic by J. Stone/E. Rubel, e.g. Oesterle and Stone 2008; Rubel et al., 2013). Regeneration can occur via mitosis of supporting cells, which may then differentiate into new hair cells and/or supporting cells, or via direct transdifferentiation (conversion) of supporting cells into hair cells, though the prevalence of these forms and the detailed signaling pathways involved likely vary across non-mammalian taxa (see text). In contrast, mammals (right) exhibit no regenerative capacity in the cochlea, although (*) some transdifferentiative regeneration appears to take place in the vestibular domain (utricle; see text). Compared to non-mammalian supporting cells, mature mammalian cochlear supporting cells exhibit thick and non-porous bands of cytoskeletal F-actin, a notable feature in the context of lost regenerative capacity (see text).

Fig. 3.. Variation in directional sensing across taxa.

A. Three fundamentally different ears-to-brain pathways are schematized. 1. Independent (non-coupled) ears sample two different points in the sound field, capturing external interaural disparities in signal timing and/or level. Strong directional sensitivity emerges only via comparison of input from the two ears by the brain, the primary basis of directional hearing in mammals. (*) Some birds also possess relatively decoupled ears. 2. Internally coupled pressure-sensitive ears also respond to external pressure disparities, but these responses are modulated by the signal at the opposite ear via the interaural canal in a time/level-dependent manner, yielding a complex but intrinsically directional response. The majority of non-mammalian terrestrial vertebrates appear to leverage such a solution; additional downstream directional processing appears to occur in many cases. (**) Phenomenologically similar solutions are evident in some arthropods (see text). 3. Ears coupled to the medium itself operate as vector sensors and are intrinsically directional. Examples include the auditory end organs of fishes and Johnston’s Organ as the primary auditory end organ in some arthropods (e.g. Drosophila). (…) As our understanding of directional acoustic sensing across taxa is drawn from a limited subset of species (and sensing in some major groups, e.g. molluscs [Burighel et al., 2011] are hardly represented), crossings between solutions and new solutions are likely. B. Schematics in (A) may be roughly conceptualized on a set of simplified axes. (***) The effective interaural distance depends on the functional distance between the ears and the speed of sound. For large distances, significant external interaural timing differences provide a highly systematic directional cue. Smaller interaural distance may be compensated by sensitivity to sufficiently high-frequency sound, the short wavelengths of which interact with even small heads, yielding relatively systematic direction-dependent interaural level differences. As both interaural separation and the upper frequency limit of sensitivity decrease, central computation of external disparities becomes less tenable and other solutions prevail. Schematized overlap across solutions denotes both exceptional organisms (e.g. non-mammals with ultrasonic hearing, aquatic megafauna), and cases in which solutions may co-occur (e.g. otophysan fishes; bone conduction hearing).

Fig. 4.. Encoding of ecologically important complex sounds – combination-sensitive neurons in echolocating bats.

The echolocating mustached bat (Pteronotus parnellii) is an auditory specialist that emits spectrotemporally complex ultrasonic calls that are reflected from prey (and other objects) and return, Doppler-shifted, milliseconds later. Receiving input from lower auditory centers (e.g. cochlear nucleus, CN, and superior olivary complex, SOC), selected auditory neurons in the midbrain (IC), thalamus (MGB), and cortex exhibit weak responses to isolated components of the echolocation call, but robust responses to combinations of source-echo call components. Across neurons, optimal combinations of component frequencies and delays represent the ranges experienced ecologically by the bat. Non-ecological combinations (e.g., high tone preceding low tone), generally do not elicit similar responsivity. Seminal observations of such “combination-sensitivity” revealed new pathways for the study of complex sound processing in the auditory system, while the study of echolocation continues to fuel discovery and innovation across many fields (see text).