Functional Neurobiology in
19 Xenopus Provides Insights
into Health and Disease
Clayton Gordy, Michael Forsthofer, Parthena
Soupiadou, Suzan Özugur, and Hans Straka
CONTENTS
19.1. Historical Background ............................................................................................................................................. 277
19.2. Past Observations in Neurobiology Using Xenopus ................................................................................................ 278
19.3. Present Status of the Field—Experimental Approaches .......................................................................................... 279
19.4. Functional Neurobiology Using In Vitro Preparations ............................................................................................. 282
19.5. Future Directions ..................................................................................................................................................... 285
Acknowledgments ................................................................................................................................................................ 286
References ............................................................................................................................................................................ 286
19.1. HISTORICAL BACKGROUND
Frogs were among the frst species used in biomedical studies,
including experimental approaches related to impairments of
brain function. Early discoveries focused on the identif cation
of general functional principles of the nervous system, which
eventually led towards insights into the origin, progression,
and potential treatment of neurological diseases in humans
(e.g. Galvani, 1791; Aubert, 1881; Ewald, 1892). For a long
time, these studies were almost exclusively conducted on
various species of adult ranid frogs, such as Rana esculenta,
temporaria, and catesbeiana, or on different species of toads,
such as bufo ( Ewald, 1892 ; Rubin, 1936 ; Guardabassi, 1955 ).
Xenopus laevis as a model species appeared only between
the 1930s and 1950s, in part driven by the increasing popularity of developmental biology (Blum and Ott, 2018). The
frst documented use of Xenopus in neurobiological research
commenced with exploring the ability to regenerate tadpole
tails (Jurand et al., 1954) and by exploring neurosecretory
and regulatory mechanisms, including the pituitary gland
(e.g. Charles, 1931; Dodd and Landgrebe, 1953). The subsequent worldwide radiation of Xenopus as a model organism for neuroscience beneftted considerably from the prior
use of ranid frog species. These latter frogs provided a large
body of morpho-physiological information on the peripheral
(PNS) and central nervous system (CNS), facilitated by the
qualitative and quantitative phylogenetic conservation of
many features of the brain and spinal cord in anurans (Llinás
and Precht, 1976). The gradual but constant transition from
ranid frogs to Xenopus as an anuran model was also driven
by the progressive classifcation of increasing numbers of
frogs as endangered species over the past 50 years, impacting
the use of the former as experimental animals (Stuart
et al., 2004). The reduced availability of many ranid frog and
other anuran species has in the meantime been more than
compensated for by Xenopus species, with the predominance
of laevis and tropicalis (Pearl et al., 2012). These species
became highly suitable for experimental settings, as they can
be made available in abundance at any time of the year due to
their easy maintenance in captivity (Nieuwkoop and Faber,
1994) across all developmental stages, ranging from embryos
to tadpoles, and adults (McNamara et al., 2018).
The systematically increasing use of Xenopus vastly
expanded anuran experimental research into diverse biological felds (Cline and Kelley, 2012). Such an expansion
is credited to the large spectrum of modern technical,
molecular, and genetic innovations that have emerged over
the past decades, which can be easily applied to Xenopus
(e.g. Pratt and Khakhalin, 2013). These latter advancements
have facilitated the probing and manipulating of behaviorally relevant neuronal circuits with considerable implications for the understanding of basic neuro-computational
and neuro-developmental aspects (Constantine-Paton and
Cline, 1998; Ruthazer and Cline, 2004), as well as clinically relevant patho-physiological conditions (Lambert and
Straka, 2012). While the overall sensory-motor capacity and
behavioral performance of Xenopus adhere to general vertebrate principles, the particular eco-physiology, such as the
permanent aquatic lifestyle, makes this species excellently
suited to study specifc sensory/motor adaptations. As one of
the major hallmark features, and in contrast to other aquatic
model species such as zebraf sh, Xenopus allows studying
the morpho-physiological transition from an animal with a
fsh-like swim style into a tetrapod with limb-based propulsion with direct relevance for the functional organization of
quadrupedal locomotion in terrestrial vertebrates (Combes
DOI: 10.1201/9781003050230-22
277
19 Xenopus Provides Insights
into Health and Disease
Clayton Gordy, Michael Forsthofer, Parthena
Soupiadou, Suzan Özugur, and Hans Straka
CONTENTS
19.1. Historical Background ............................................................................................................................................. 277
19.2. Past Observations in Neurobiology Using Xenopus ................................................................................................ 278
19.3. Present Status of the Field—Experimental Approaches .......................................................................................... 279
19.4. Functional Neurobiology Using In Vitro Preparations ............................................................................................. 282
19.5. Future Directions ..................................................................................................................................................... 285
Acknowledgments ................................................................................................................................................................ 286
References ............................................................................................................................................................................ 286
19.1. HISTORICAL BACKGROUND
Frogs were among the frst species used in biomedical studies,
including experimental approaches related to impairments of
brain function. Early discoveries focused on the identif cation
of general functional principles of the nervous system, which
eventually led towards insights into the origin, progression,
and potential treatment of neurological diseases in humans
(e.g. Galvani, 1791; Aubert, 1881; Ewald, 1892). For a long
time, these studies were almost exclusively conducted on
various species of adult ranid frogs, such as Rana esculenta,
temporaria, and catesbeiana, or on different species of toads,
such as bufo ( Ewald, 1892 ; Rubin, 1936 ; Guardabassi, 1955 ).
Xenopus laevis as a model species appeared only between
the 1930s and 1950s, in part driven by the increasing popularity of developmental biology (Blum and Ott, 2018). The
frst documented use of Xenopus in neurobiological research
commenced with exploring the ability to regenerate tadpole
tails (Jurand et al., 1954) and by exploring neurosecretory
and regulatory mechanisms, including the pituitary gland
(e.g. Charles, 1931; Dodd and Landgrebe, 1953). The subsequent worldwide radiation of Xenopus as a model organism for neuroscience beneftted considerably from the prior
use of ranid frog species. These latter frogs provided a large
body of morpho-physiological information on the peripheral
(PNS) and central nervous system (CNS), facilitated by the
qualitative and quantitative phylogenetic conservation of
many features of the brain and spinal cord in anurans (Llinás
and Precht, 1976). The gradual but constant transition from
ranid frogs to Xenopus as an anuran model was also driven
by the progressive classifcation of increasing numbers of
frogs as endangered species over the past 50 years, impacting
the use of the former as experimental animals (Stuart
et al., 2004). The reduced availability of many ranid frog and
other anuran species has in the meantime been more than
compensated for by Xenopus species, with the predominance
of laevis and tropicalis (Pearl et al., 2012). These species
became highly suitable for experimental settings, as they can
be made available in abundance at any time of the year due to
their easy maintenance in captivity (Nieuwkoop and Faber,
1994) across all developmental stages, ranging from embryos
to tadpoles, and adults (McNamara et al., 2018).
The systematically increasing use of Xenopus vastly
expanded anuran experimental research into diverse biological felds (Cline and Kelley, 2012). Such an expansion
is credited to the large spectrum of modern technical,
molecular, and genetic innovations that have emerged over
the past decades, which can be easily applied to Xenopus
(e.g. Pratt and Khakhalin, 2013). These latter advancements
have facilitated the probing and manipulating of behaviorally relevant neuronal circuits with considerable implications for the understanding of basic neuro-computational
and neuro-developmental aspects (Constantine-Paton and
Cline, 1998; Ruthazer and Cline, 2004), as well as clinically relevant patho-physiological conditions (Lambert and
Straka, 2012). While the overall sensory-motor capacity and
behavioral performance of Xenopus adhere to general vertebrate principles, the particular eco-physiology, such as the
permanent aquatic lifestyle, makes this species excellently
suited to study specifc sensory/motor adaptations. As one of
the major hallmark features, and in contrast to other aquatic
model species such as zebraf sh, Xenopus allows studying
the morpho-physiological transition from an animal with a
fsh-like swim style into a tetrapod with limb-based propulsion with direct relevance for the functional organization of
quadrupedal locomotion in terrestrial vertebrates (Combes
DOI: 10.1201/9781003050230-22
277