404
The level of hair cell damage can depend on ototoxin concentration (Yan et al. 1991 ;
Ton and Parng 2005 ; Hernández et al. 2006 ; Olivari et al. 2008 ) and exposure time
(Song et al. 1995 ). Susceptibility of inner ear hair cells may also differ based on their
location. For example, intramuscular gentamicin injections led to hair cell damage in
the caudal portion of the saccule and the striolar region of the utricle in the goldfi sh ear
(Ramcharitar and Selckmann 2010 ). In oscars, the striolar regions of both the utricles
and lagenae were sensitive to gentamicin (Yan et al. 1991 ), while gentamicin can
induce damage across the entire saccule and in both striolar and extrastriolar areas of
the utricle in zebrafi sh (Uribe et al. 2013b ). It is unclear if such differences are due to
physiological differences between hair cell types or species, or due to experimental
differences, e.g., gentamicin concentrations or injection methods. Differential susceptibility may also occur in the lateral line system of fi shes. It was fi rst reported that
gentamicin produces damage in the canal but not the superfi cial neuromasts of the lateral line (Song et al. 1995 ). Recently, new data shows that gentamicin can kill hair cells
in both canal and superfi cial neuromasts (Van Trump et al. 2010 ), suggesting that caution should be used when using aminoglycosides in behavioral studies of the lateral
line (Brown et al. 2011 ). Another factor that should be taken into account is the ontogenic stage as ototoxic susceptibility in the zebrafi sh lateral line can increase as fi sh
undergo development (Harris et al. 2003 ; Murakami et al. 2003 ; Santos et al. 2006 ).
Heavy metals and platinum containing chemotherapy drugs can also kill inner ear
and lateral line hair cells. In larval zebrafi sh, lateral line hair cells and neuromast supporting cells are damaged by copper exposure in a concentration dependent manner
(Hernández et al. 2006 , 2007 ). In zebrafi sh, the platinum based chemotherapy agent
cisplatin acts as an ototoxin (Ton and Parng 2005 ; Ou et al. 2007 ; Chiu et al. 2008 ;
Owens et al. 2008 ; Giari et al. 2012 ). Cisplatin can cause greater damage to zebrafi sh
inner ear hair cells than those in the lateral line (Giari et al. 2012 ). Ototoxicity increases
when cisplatin is used in conjunction with other chemicals including the solvent
DMSO and some anti-cancer drugs (Hirose et al. 2011 ; Uribe et al. 2013a ).
Zebrafi sh lateral line studies are now used to discover otoprotectant chemicals that
counteract ototoxins (Coffi n et al. 2009 , 2010 , 2013 ; Ou et al. 2010 ; Esterberg et al.
2013 ). These studies have identifi ed many promising compounds that can counteract
cisplatin and aminoglycoside modulated ototoxicity (Kim et al. 2008 ; Owens et al.
2008 ; Ou et al. 2012 ; Shin et al. 2012 ; Vlasits et al. 2012 ). Thus, fi sh models are now
not only successfully used for identifying ototoxins, but are rapidly becoming powerful
new tools for identifying pharmaceutical leads that may prevent damage to hair cells.
5 Consequences of Vestibular and Lateral Line Defi cits
Large-scale mutagenesis screens have discovered zebrafi sh mutants that are morphologically normal but exhibit balance defi cits (Whitfi eld et al. 1996 ; Nicolson 2005 ).
Loss of vestibular function in fi shes can be identifi ed via swimming behavior, the
potentiated dorsal light refl ex, the acoustic/vibrational startle refl ex, monitoring neuronal activity in the mid- and hind-brain, and measuring microphonic potentials of
M.E. Smith and J.D. Monroe
The level of hair cell damage can depend on ototoxin concentration (Yan et al. 1991 ;
Ton and Parng 2005 ; Hernández et al. 2006 ; Olivari et al. 2008 ) and exposure time
(Song et al. 1995 ). Susceptibility of inner ear hair cells may also differ based on their
location. For example, intramuscular gentamicin injections led to hair cell damage in
the caudal portion of the saccule and the striolar region of the utricle in the goldfi sh ear
(Ramcharitar and Selckmann 2010 ). In oscars, the striolar regions of both the utricles
and lagenae were sensitive to gentamicin (Yan et al. 1991 ), while gentamicin can
induce damage across the entire saccule and in both striolar and extrastriolar areas of
the utricle in zebrafi sh (Uribe et al. 2013b ). It is unclear if such differences are due to
physiological differences between hair cell types or species, or due to experimental
differences, e.g., gentamicin concentrations or injection methods. Differential susceptibility may also occur in the lateral line system of fi shes. It was fi rst reported that
gentamicin produces damage in the canal but not the superfi cial neuromasts of the lateral line (Song et al. 1995 ). Recently, new data shows that gentamicin can kill hair cells
in both canal and superfi cial neuromasts (Van Trump et al. 2010 ), suggesting that caution should be used when using aminoglycosides in behavioral studies of the lateral
line (Brown et al. 2011 ). Another factor that should be taken into account is the ontogenic stage as ototoxic susceptibility in the zebrafi sh lateral line can increase as fi sh
undergo development (Harris et al. 2003 ; Murakami et al. 2003 ; Santos et al. 2006 ).
Heavy metals and platinum containing chemotherapy drugs can also kill inner ear
and lateral line hair cells. In larval zebrafi sh, lateral line hair cells and neuromast supporting cells are damaged by copper exposure in a concentration dependent manner
(Hernández et al. 2006 , 2007 ). In zebrafi sh, the platinum based chemotherapy agent
cisplatin acts as an ototoxin (Ton and Parng 2005 ; Ou et al. 2007 ; Chiu et al. 2008 ;
Owens et al. 2008 ; Giari et al. 2012 ). Cisplatin can cause greater damage to zebrafi sh
inner ear hair cells than those in the lateral line (Giari et al. 2012 ). Ototoxicity increases
when cisplatin is used in conjunction with other chemicals including the solvent
DMSO and some anti-cancer drugs (Hirose et al. 2011 ; Uribe et al. 2013a ).
Zebrafi sh lateral line studies are now used to discover otoprotectant chemicals that
counteract ototoxins (Coffi n et al. 2009 , 2010 , 2013 ; Ou et al. 2010 ; Esterberg et al.
2013 ). These studies have identifi ed many promising compounds that can counteract
cisplatin and aminoglycoside modulated ototoxicity (Kim et al. 2008 ; Owens et al.
2008 ; Ou et al. 2012 ; Shin et al. 2012 ; Vlasits et al. 2012 ). Thus, fi sh models are now
not only successfully used for identifying ototoxins, but are rapidly becoming powerful
new tools for identifying pharmaceutical leads that may prevent damage to hair cells.
5 Consequences of Vestibular and Lateral Line Defi cits
Large-scale mutagenesis screens have discovered zebrafi sh mutants that are morphologically normal but exhibit balance defi cits (Whitfi eld et al. 1996 ; Nicolson 2005 ).
Loss of vestibular function in fi shes can be identifi ed via swimming behavior, the
potentiated dorsal light refl ex, the acoustic/vibrational startle refl ex, monitoring neuronal activity in the mid- and hind-brain, and measuring microphonic potentials of
M.E. Smith and J.D. Monroe