278
Xenopus
et al., 2004). The remarkable shapeshifting capacity during metamorphosis, even though inferior and irreversible
compared to the extraterrestrial species of the changelings
(Carey, 1999), is accompanied by an equally extensive neuronal restructuration and adjustment of motor prof ciency.
This reorganization thus offers unique insight into the
extent of adaptive plasticity of the vertebrate nervous system, making Xenopus an outstanding model to study major
neurobiological questions. Xenopus is therefore well suited
to identify functionally relevant aspects of neurobiological
systems, which is fundamental for the identif cation and
understanding of vertebrate diseases, including those present in humans.
19.2. PAST OBSERVATIONS IN
NEUROBIOLOGY USING XENOPUS
Most neuroscientifc discoveries in frogs resulted from complementary work on ranid species and Xenopus. From early
on, these studies focused on basic principles, such as anatomical connectivity, signaling patterns, neuronal plasticity,
and behavior, which are summarized in the comprehensive
masterpiece of Nieuwenhuys et al. (1998). Collectively,
these studies provided the foundational understanding for
functional aspects of the anuran nervous system (Figure
19.1A1–5), though often without particular focus on topics
related to health and disease. Novel tract tracing and intracellular recording techniques along with manipulations of
embryonic tissue allowed the exploration of the organization and capacity of inducing plastic adaptations in a variety
of sensory systems. While not necessarily exhaustive, this
section highlights major discoveries of neurobiological principles obtained in anurans, with emphasis on the erstwhile
available state-of-the-art methodologies and outcomes.
Early research on cranial sensory organs and associated
central targets produced multiple ground-breaking f ndings
on topics of neuroanatomy and connectivity, largely based
on cut-and-paste tissue experiments (Fritzsch et al., 2019).
Hallmark studies included the discovery of visual f eld representations in the central nervous system (Sperry, 1944,
1956). Combining optic nerve transections with behavioral
assessment in adult frogs, a remarkable reconnection of
optic nerve f bers with proper areas of the optic tectum was
observed, which permitted restoration of visual capabilities.
This culminated in sets of experiments in which eyes were
rotated by 180°, effectively fipping and mirroring the retina.
At that time, most behavioral experiments were limited to
simple categorical evaluations, such as observing the direction of a guided behavior in response to an external stimulus.
Eye-rotated animals were presented with prey in a specif c
part of their visual feld. This elicited capture responses
which were oriented in the opposite direction to the location
of the prey, confrming that the visual feld had been mirrored along with the retina (Sperry, 1944). Although initial
experiments were performed in urodeles, the outcome was
validated in frogs (Sperry, 1944). Combining such targeted
perturbations and behavioral assays therefore demonstrated
the presence of peripheral subdivisions and tectal topographies based on the identity of retinal subregions (Sperry,
1956) (Figure 19.1A1). Further exploration of visual system connectivity continued with the milestone experiments
by Constantine-Paton and Law (1978), which combined
embryonic manipulations and neuronal tract/nerve tracings. Embryonic transplantation of an optic anlage onto
Rana embryos generated three-eyed animals and allowed
the evaluation of the connectivity pattern and neural targeting strategy of the supernumerary eye in the midbrain.
Available techniques at that time, such as tracing with
radioactive amino acids, revealed that the third eye generated discrete alternating columns innervated by either one
of the other eyes along the tectal surface (Constantine-Paton
and Law, 1978). By expanding the fndings on principles
of visual connectivity specifcation, these results not only
uplifted frogs into the realm of animal models with broad
neurobiological relevance, but also demonstrated the suitability of these animals for determining key concepts of
development and function of sensory systems (ConstantinePaton and Law, 1978; Fritzsch et al., 2019).
The early contributions of Xenopus were no less prolif c
than those obtained in ranid frogs and further illustrated the
ease of assessing sensory system networks and function in
these species. The simplicity of embryonic manipulations
in frogs, particularly in Xenopus laevis, allowed generating animals with all-nasal or all-temporal retinas by grafting together halves of eye primordia in embryos before the
initial innervation of the tectum (Gaze et al., 1963). With
the advent of robust and reliable electrophysiological recordings, it was possible to probe single-cell neuronal activity of
tectal neurons in adult frogs after metamorphosis, providing an objective functional assessment of sensory inputs into
the midbrain. Visual feld representation across the tectal
surface in such animals revealed that each half-retina was
mapped onto the tectum in a mirror-like fashion (Gaze et al.,
1963), leading to the conclusion that each half-retina reorganizes itself into a small full retina, with respective nasal and
temporal identities (Meyer and Sperry, 1976). The biological
implications of these results, particularly those obtained in
Xenopus, emphasized the remarkable amount of plasticity
and reorganizational capacity of developmental processes as
opposed to regeneration in adult animals (Meyer and Sperry,
1976). Moreover, these studies also showed the analytical
power of electrophysiological recordings in the quest to
decipher central representations of the sensory periphery.
Combining early embryonic manipulations and tract
tracing in Xenopus also helped exploring other sensory and
motor systems as well as axonal pathf nding mechanisms,
which are at the origin of the ontogenetic assembly of circuits. Accordingly, eye primordia grafted onto the dorsal
trunk (Giorgi and van der Loos, 1978) demonstrated correct development of corresponding connections through
the spinal cord by visualizing retinal ganglion cell neurites
in the brain. Despite the caudally displaced origin of optic
nerve fbers, the grafted eye innervated the correct tectal target site, provided that both innate eyes were ablated
Xenopus
et al., 2004). The remarkable shapeshifting capacity during metamorphosis, even though inferior and irreversible
compared to the extraterrestrial species of the changelings
(Carey, 1999), is accompanied by an equally extensive neuronal restructuration and adjustment of motor prof ciency.
This reorganization thus offers unique insight into the
extent of adaptive plasticity of the vertebrate nervous system, making Xenopus an outstanding model to study major
neurobiological questions. Xenopus is therefore well suited
to identify functionally relevant aspects of neurobiological
systems, which is fundamental for the identif cation and
understanding of vertebrate diseases, including those present in humans.
19.2. PAST OBSERVATIONS IN
NEUROBIOLOGY USING XENOPUS
Most neuroscientifc discoveries in frogs resulted from complementary work on ranid species and Xenopus. From early
on, these studies focused on basic principles, such as anatomical connectivity, signaling patterns, neuronal plasticity,
and behavior, which are summarized in the comprehensive
masterpiece of Nieuwenhuys et al. (1998). Collectively,
these studies provided the foundational understanding for
functional aspects of the anuran nervous system (Figure
19.1A1–5), though often without particular focus on topics
related to health and disease. Novel tract tracing and intracellular recording techniques along with manipulations of
embryonic tissue allowed the exploration of the organization and capacity of inducing plastic adaptations in a variety
of sensory systems. While not necessarily exhaustive, this
section highlights major discoveries of neurobiological principles obtained in anurans, with emphasis on the erstwhile
available state-of-the-art methodologies and outcomes.
Early research on cranial sensory organs and associated
central targets produced multiple ground-breaking f ndings
on topics of neuroanatomy and connectivity, largely based
on cut-and-paste tissue experiments (Fritzsch et al., 2019).
Hallmark studies included the discovery of visual f eld representations in the central nervous system (Sperry, 1944,
1956). Combining optic nerve transections with behavioral
assessment in adult frogs, a remarkable reconnection of
optic nerve f bers with proper areas of the optic tectum was
observed, which permitted restoration of visual capabilities.
This culminated in sets of experiments in which eyes were
rotated by 180°, effectively fipping and mirroring the retina.
At that time, most behavioral experiments were limited to
simple categorical evaluations, such as observing the direction of a guided behavior in response to an external stimulus.
Eye-rotated animals were presented with prey in a specif c
part of their visual feld. This elicited capture responses
which were oriented in the opposite direction to the location
of the prey, confrming that the visual feld had been mirrored along with the retina (Sperry, 1944). Although initial
experiments were performed in urodeles, the outcome was
validated in frogs (Sperry, 1944). Combining such targeted
perturbations and behavioral assays therefore demonstrated
the presence of peripheral subdivisions and tectal topographies based on the identity of retinal subregions (Sperry,
1956) (Figure 19.1A1). Further exploration of visual system connectivity continued with the milestone experiments
by Constantine-Paton and Law (1978), which combined
embryonic manipulations and neuronal tract/nerve tracings. Embryonic transplantation of an optic anlage onto
Rana embryos generated three-eyed animals and allowed
the evaluation of the connectivity pattern and neural targeting strategy of the supernumerary eye in the midbrain.
Available techniques at that time, such as tracing with
radioactive amino acids, revealed that the third eye generated discrete alternating columns innervated by either one
of the other eyes along the tectal surface (Constantine-Paton
and Law, 1978). By expanding the fndings on principles
of visual connectivity specifcation, these results not only
uplifted frogs into the realm of animal models with broad
neurobiological relevance, but also demonstrated the suitability of these animals for determining key concepts of
development and function of sensory systems (ConstantinePaton and Law, 1978; Fritzsch et al., 2019).
The early contributions of Xenopus were no less prolif c
than those obtained in ranid frogs and further illustrated the
ease of assessing sensory system networks and function in
these species. The simplicity of embryonic manipulations
in frogs, particularly in Xenopus laevis, allowed generating animals with all-nasal or all-temporal retinas by grafting together halves of eye primordia in embryos before the
initial innervation of the tectum (Gaze et al., 1963). With
the advent of robust and reliable electrophysiological recordings, it was possible to probe single-cell neuronal activity of
tectal neurons in adult frogs after metamorphosis, providing an objective functional assessment of sensory inputs into
the midbrain. Visual feld representation across the tectal
surface in such animals revealed that each half-retina was
mapped onto the tectum in a mirror-like fashion (Gaze et al.,
1963), leading to the conclusion that each half-retina reorganizes itself into a small full retina, with respective nasal and
temporal identities (Meyer and Sperry, 1976). The biological
implications of these results, particularly those obtained in
Xenopus, emphasized the remarkable amount of plasticity
and reorganizational capacity of developmental processes as
opposed to regeneration in adult animals (Meyer and Sperry,
1976). Moreover, these studies also showed the analytical
power of electrophysiological recordings in the quest to
decipher central representations of the sensory periphery.
Combining early embryonic manipulations and tract
tracing in Xenopus also helped exploring other sensory and
motor systems as well as axonal pathf nding mechanisms,
which are at the origin of the ontogenetic assembly of circuits. Accordingly, eye primordia grafted onto the dorsal
trunk (Giorgi and van der Loos, 1978) demonstrated correct development of corresponding connections through
the spinal cord by visualizing retinal ganglion cell neurites
in the brain. Despite the caudally displaced origin of optic
nerve fbers, the grafted eye innervated the correct tectal target site, provided that both innate eyes were ablated