420
1 Introduction
The sensory arsenal of fi shes has likely contributed to their tremendous evolutionary success, allowing them to thrive in diverse habitats. Fishes are armed with
chemical, visual, tactile, auditory, and vestibular sensory apparati that are morphologically and functionally comparable to those found in other vertebrate taxa.
Sensory hair cells serve as receptors in both the auditory and vestibular systems,
and in an additional hair cell-based system, the mechanosensory lateral line found
in fi shes and aquatic amphibians. Together, these sensory systems operate in concert
to provide fi shes with a comprehensive picture of the ambient environment.
Multisensory integration is a critical feature for successful execution of a host of
fi sh behaviors such as prey detection, predator avoidance, and escape responses
(Collins et al. 2003 ; Mirjany et al. 2011 ; Van Trump and McHenry 2013 ).
Here, we review studies of fi sh hair cell systems, with a focus on how chemical
ototoxins, substances that damage hair cells, have been employed as tools to enhance
fi sh hair cell research. We fi rst examine how ototoxins, combined with detailed
morphological assessment, have informed our understanding of vertebrate hair cell
heterogeneity and evolution. We then look at studies of mechanosensory-mediated
behaviors in fi shes, again relying on selective ablation with ototoxins to determine
the relative contribution of these systems to fi sh behavior. In addition to understanding fi sh mechanosensation, the inner ear and lateral line have been deployed as
valuable models for human auditory studies. Section 4 describes some of this biomedical research, both the cellular understanding of ototoxicity itself and the use of
ototoxic tools for investigating hair cell regeneration. The bulk of both behavioral
and biomedical studies use known ototoxins, such as aminoglycoside antibiotics,
but several studies suggest that many other compounds are potentially ototoxic
(Hirose et al. 2011 ). We conclude with a brief description of newly identifi ed putative ototoxins, specifi cally those found in the aquatic environment, and with some
of the unresolved questions that ototoxic research may help answer in the future.
The inner ears of fi shes comprise three semicircular canals, each with associated
sensory cristae and three otolithic end organs, the saccule, utricle, and lagena (Fig.
1 ; Popper 1977 , 1978 ; Popper and Lu 2000 ). All end organs contain populations of
sensory hair cells interdigitated with non-sensory supporting cells. The semicircular
canals and the utricle primarily subserve vestibular functions, although the utricle
plays an auditory role in some taxa. On the other hand, the saccule is the primary
auditory end organ in most species, while the function of the lagena is poorly understood (Popper and Lu 2000 ). The vestibular organs provide positional information,
while the auditory organ(s) allow the fi sh to detect both abiotic (e.g., rainfall or wave
noise) and biotic (e.g., conspecifi c calls) acoustic stimuli of biological relevance.
Psychophysical studies in the late 1990s demonstrated that fi shes are capable of
auditory scene analysis, and this fi nding supports the hypothesis that they are broadly
sensitive to sound stimuli from diverse sources (Fay 1998 ; Fay and Popper 2012 ).
The second major hair cell-based system in fi shes, the lateral line system, is
responsive to mechanosensory stimulation in a relatively low and narrow frequency
range of ~50–200 Hz (Kalmijn 1988 ; reviewed in Coombs et al. 2014 ). In the lateral
A.B. Coffi n and J. Ramcharitar
1 Introduction
The sensory arsenal of fi shes has likely contributed to their tremendous evolutionary success, allowing them to thrive in diverse habitats. Fishes are armed with
chemical, visual, tactile, auditory, and vestibular sensory apparati that are morphologically and functionally comparable to those found in other vertebrate taxa.
Sensory hair cells serve as receptors in both the auditory and vestibular systems,
and in an additional hair cell-based system, the mechanosensory lateral line found
in fi shes and aquatic amphibians. Together, these sensory systems operate in concert
to provide fi shes with a comprehensive picture of the ambient environment.
Multisensory integration is a critical feature for successful execution of a host of
fi sh behaviors such as prey detection, predator avoidance, and escape responses
(Collins et al. 2003 ; Mirjany et al. 2011 ; Van Trump and McHenry 2013 ).
Here, we review studies of fi sh hair cell systems, with a focus on how chemical
ototoxins, substances that damage hair cells, have been employed as tools to enhance
fi sh hair cell research. We fi rst examine how ototoxins, combined with detailed
morphological assessment, have informed our understanding of vertebrate hair cell
heterogeneity and evolution. We then look at studies of mechanosensory-mediated
behaviors in fi shes, again relying on selective ablation with ototoxins to determine
the relative contribution of these systems to fi sh behavior. In addition to understanding fi sh mechanosensation, the inner ear and lateral line have been deployed as
valuable models for human auditory studies. Section 4 describes some of this biomedical research, both the cellular understanding of ototoxicity itself and the use of
ototoxic tools for investigating hair cell regeneration. The bulk of both behavioral
and biomedical studies use known ototoxins, such as aminoglycoside antibiotics,
but several studies suggest that many other compounds are potentially ototoxic
(Hirose et al. 2011 ). We conclude with a brief description of newly identifi ed putative ototoxins, specifi cally those found in the aquatic environment, and with some
of the unresolved questions that ototoxic research may help answer in the future.
The inner ears of fi shes comprise three semicircular canals, each with associated
sensory cristae and three otolithic end organs, the saccule, utricle, and lagena (Fig.
1 ; Popper 1977 , 1978 ; Popper and Lu 2000 ). All end organs contain populations of
sensory hair cells interdigitated with non-sensory supporting cells. The semicircular
canals and the utricle primarily subserve vestibular functions, although the utricle
plays an auditory role in some taxa. On the other hand, the saccule is the primary
auditory end organ in most species, while the function of the lagena is poorly understood (Popper and Lu 2000 ). The vestibular organs provide positional information,
while the auditory organ(s) allow the fi sh to detect both abiotic (e.g., rainfall or wave
noise) and biotic (e.g., conspecifi c calls) acoustic stimuli of biological relevance.
Psychophysical studies in the late 1990s demonstrated that fi shes are capable of
auditory scene analysis, and this fi nding supports the hypothesis that they are broadly
sensitive to sound stimuli from diverse sources (Fay 1998 ; Fay and Popper 2012 ).
The second major hair cell-based system in fi shes, the lateral line system, is
responsive to mechanosensory stimulation in a relatively low and narrow frequency
range of ~50–200 Hz (Kalmijn 1988 ; reviewed in Coombs et al. 2014 ). In the lateral
A.B. Coffi n and J. Ramcharitar