Molecular and Cellular Endocrinology 518 (2020) 110986

Contents lists available at ScienceDirect

Molecular and Cellular Endocrinology

journal homepage: www.elsevier.com/locate/mce

Thermoregulation in fish
Martin Haesemeyer
The Ohio State University College of Medicine, Department of Neuroscience, Columbus, OH, USA

A R T I C L E I N F O A B S T R A C T

Keywords: Thermoregulation is critical for survival and animals therefore employ strategies to keep their body temperature
Thermoregulation within a physiological range. As ectotherms, fish exclusively rely on behavioral strategies for thermoregulation.
Fish Different species of fish seek out their specific optimal temperatures through thermal navigation by biasing
Zebrafish
behavioral output based on experienced environmental temperatures. Like other vertebrates, fish sense water
Behavior
Circuit
temperature using thermoreceptors in trigeminal and dorsal root ganglia neurons that innervate the skin. Recent
Ethology research in larval zebrafish has revealed how neural circuits subsequently transform this sensation of temper­
ature into thermoregulatory behaviors. Across fish species, thermoregulatory strategies rely on a modulation of
swim vigor based on current temperature and a modulation of turning based on temperature change. Interest­
ingly, temperature preferences are not fixed but depend on other environmental cues and internal states. The
following review is intended as an overview on the current knowledge as well as open questions in fish
thermoregulation.

1. Introduction recent success of the zebrafish model in informing clinically relevant

Metabolic rate and function strongly depend on temperature. While
temperatures below critical values limit cellular metabolism and ner­
vous system function, high temperatures can lead to protein instability
and cell death. Animals therefore evolved strategies to regulate their
body temperature. These include behavioral strategies, such as seeking
out environments of preferred temperature, as well as autonomous
strategies employed in endothermic animals, such as heat generation by
brown fat or muscle shivering. However, even animals that can regulate
their own body temperature generally employ behavioral strategies as
well to conserve energy and to reduce water expenditure (Crawshaw and
Stitt, 1975; Tan and Knight, 2018). Also, while muscle shivering ther­
mogenesis is part of the autonomic regulation of body temperature in
endotherms, it essentially co-opts a behavioral process. Interestingly,
temperature setpoints are flexible and adjust to metabolic needs of the
animal as seen in the circadian fluctuations of core body temperature in
mammals (Refinetti, 1999). A particularly striking example of temper­
ature setpoint changes is the induction of fever, a process conserved
across many animal groups including ectotherms (Nakamura, 2011;
Rakus et al., 2017). Furthermore, dysregulation of thermal perception
and core body temperature regulation have been found to be associated
with both psychiatric disorders such as Tourette’s syndrome (Kessler,
2002) as well as pharmacological agents that are used to treat neuro­
psychiatric disorders (Löffler et al., 2008; Singer, 2010). Given the
research through mutant analysis and drug screening (Cully, 2019),
studying temperature perception in fish could have translational po­
tential here as well.
In the following article I review current knowledge on thermoregu­
latory behaviors in fish as well as the neural circuits controlling these
behaviors. I will start with an ethological perspective, review sensory
systems and central processing, and lay out interesting questions related
to the flexibility of thermoregulation. Thermoregulatory strategies are
often conserved across phyla, and I will therefore touch on comparative
aspects as well. In the end I will provide a brief outlook on potentially
fruitful future research directions.
2. The behavioral and neural basis of fish thermoregulation
2.1. Ethological perspective
Fish are largely ectothermic animals, with the exception of some
species of tuna and sharks which can conserve and redistribute meta­
bolic heat to raise their core body temperature (Carey et al., 1971). This
means that unless fish live in very stable environments, their core body
temperature fluctuates with the temperature of the water they occupy.
Therefore, even though many fish species can tolerate a wide tempera­
ture range, they rely on navigational strategies to keep their body
temperature near a metabolic and reproductive optimum (Kennedy and

E-mail address: haesemeyer.1@osu.edu.

https://doi.org/10.1016/j.mce.2020.110986
Received 7 December 2019; Received in revised form 7 August 2020; Accepted 9 August 2020
Available online 22 August 2020
0303-7207/© 2020 Elsevier B.V. All rights reserved.
M. Haesemeyer Molecular and Cellular Endocrinology 518 (2020) 110986

Mihursky, 1967). streams into rivers. In the case of larval zebrafish, habitat temperatures
Given the vast differences in temperature across water habitats on in the wild fluctuate widely since they live in shallow pools and streams
earth, ranging from near freezing in arctic regions to 30 ◦ C and higher in which can be easily heated locally by sunlight (Engeszer et al., 2007;
the tropics, it is not surprising that preferred temperatures vary widely Roger, 1996). This means that fish likely evolved navigational strategies
across fish species (Coutant, 1977). This suggests a co-adaptation be­ that allow them to seek out preferred temperatures in their habitat at
tween metabolic strategies and temperature preferences. Indeed, there is which their metabolism functions optimally.
evidence for such co-adaptation. E.g., vertical temperature differences in
Lake Stechlin have allowed sympatric speciation in the common ven­
2.2. Behavioral strategies
dace. Here, C. albula and C. fontanae occupy the same pelagic feeding
zone but have slightly different vertical distribution with metabolic
To reach their preferred water temperature, fish need to employ
adaptations to different temperature optima (Ohlberger et al., 2008). In
navigational strategies that maximize their time in the preferred envi­
Atlantic cod on the other hand there is a segregation in hemoglobin
ronment while allowing them to avoid harmful conditions. Fish indeed
polymorphisms with a HbI2 allele dominating in northern populations
possess such behavioral strategies since they have been demonstrated to
and a HbI1 allele dominating in warmer areas (Petersen and Steffensen,
aggregate in fairly narrow temperature ranges within their habitat and
2003). In the laboratory, cod homozygous for the HbI2 allele prefer
these preferences are often stable across years (Gammon, 1998).
lower temperature water (~8 ◦ C) than cod homozygous for the HbI1
Furthermore, fish can quickly adapt to changing conditions. Atlantic cod
allele (~15 ◦ C) (Petersen and Steffensen, 2003). This change in prefer­
will migrate towards the shore when changes in wind direction push
ence is aligned with differences in oxygen affinity in the two hemoglobin
warmer surface water out into the open ocean (Rose and Leggett, 1988).
variants, where HbI2 has higher oxygen affinity at lower temperatures,
Another opportunity to study thermal navigation in the wild is offered
while HbI1 is better at binding oxygen at higher temperatures (Brix
by warm plumes from power plant cooling water effluents into lakes and
et al., 1998; Karpov and Novikov, 1980). This suggests that even within
streams (Fig. 1A). Studies conducted in Lake Monona revealed that
a species, as the metabolism adapts to the environment, behavioral
different species of fish aggregate in narrow temperature zones within or
preferences change as well. This however is not always the case, as
away from the warm outflow area of a power plant (Neill and Magnuson,
temperature preferenda recorded within the lab diverge from general
1974). These distributions were notably stable even when food abun­
habitat temperatures for some fish species suggesting that adaptation
dance was higher in the outflow area, indicating that fish will avoid too
isn’t necessarily absolute (Beitinger and Fitzpatrick, 1979).
warm waters even if this reduces their access to food (Neill and Mag­
Importantly, temperatures in natural habitats of fish fluctuate across
nuson, 1974). Similarly, trout in Lake Leydoux restrict their distribution
both space and time. These fluctuations arise due to changes in wind
to cool areas of the lake (12–16 ◦ C) while the water reaches tempera­
direction, vertical temperature differences or influxes of cold or warm
tures greater than 26 ◦ C near the shore. Trout are able to maintain this

Fig. 1. Thermoregulatory behaviors. A:

Heated outflow from power plants or in­
fluxes of cold streams offer the opportunity
to study how different fish species distribute
within a temperature gradient in their nat­
ural habitat. B: Artificially created tempera­
ture gradients within the lab allow studying
navigation behavior in great detail and in
the absence of other potentially confounding
cues. C: In such controlled settings detailed
behavioral kinematics (such as the distance
d traveled in a swim or the turn angle α) can
be extracted and modeled in dependence of
previous sensory experience such as the
resting temperature T0 before the swim or
the previously experienced change in tem­
perature ΔT).. D: Work across fish (and in
fact many species navigating sensory gradi­
ents) has revealed a general strategy which
consists of modulating movement vigor by
current temperature and turning by tem­
perature changes.

2
M. Haesemeyer
distribution in spite of swimming average distances larger than 100 m a
day, indicating active avoidance of areas of warm water (Goyer et al.,
2014). Furthermore, models based on the migration of salmon suggest
that these fish might use water temperature profiles to direct their
long-range migration (Booker et al., 2008; Byron and Burke, 2014). This
suggests that fish not only use temperature to navigate thermal profiles
themselves but that they can also use such information to accomplish
geographical navigation in general.
Observing thermal navigation in the wild is critical to establish that
fish actually face thermal challenges in their habitat and that they
attempt to move to ideal temperatures under natural conditions. How­
ever, studying thermal navigation in the laboratory is essential to go
beyond establishing temperature preferences and investigate the un­
derlying behavioral algorithms animals use to navigate. In particular,
laboratory experiments can disambiguate influences of cues learned to
be correlated with temperature through experience or evolution (“pre­
dictive thermal navigation”) from navigational strategies that depend on
temperature sensation in the current environment (“reactive thermal
navigation”) (Neill, 1979). And indeed, many fish species have been
shown to seek out preferred temperatures in laboratory settings. In an
elegant series of experiments Neill and Magnuson allowed fish to control
the temperature of their tanks to determine preferred temperature (Neill
and Magnuson, 1974; Neill et al., 1972). Namely, whenever the fish
swam into one side of a two-tank system, water temperature was
increased, while swimming into the other side would lead to decreases
in water temperature (Neill et al., 1972). Fish could thereby control the
tank water temperature. Intriguingly, the temperature fish chose to set
the system to would largely agree with the temperature they preferred in
their natural habitat (Neill and Magnuson, 1974). This suggests that fish
can indeed navigate thermal gradients to find their optimal temperature.
However, the strategy developed by fish in this paradigm is likely a mix
of reactive and predictive modes.
These experiments clearly reveal that fish can seek out preferred
temperatures, but how do they accomplish this task? Experiments
recording fish behavior in relation to water temperature revealed that in
changing thermal environments such as a heat gradient, fish tend to
display the lowest movement vigor close to their preferred temperature
with swim vigor increasing as temperature departs from preferred
values (Ivlev, 1960; Sullivan, 1954). This points to a strategy of “diffu­
sional trapping” or “orthokinesis”. Such a strategy by itself will indeed
lead to accumulation near the preferred temperature (since animals tend
to rest there) and away from less ideal conditions (since animals tend to
vigorously move and thereby leave those areas), however it is not
effective in avoiding noxious conditions (Fraenkel and Gunn, 1961). By
itself it is therefore far from an ideal strategy for survival (Neill, 1979).
However, computer simulations suggest that adding a strategy based on
increased turning when temperatures are worsening, in other words,
when the change in temperature is unfavorable, could explain thermal
preferences observed in fish without risking increased exposure to
noxious conditions (Neill, 1979). Notably, these strategies are akin to
the biased random walk displayed during bacterial chemotaxis (Alt,
1980; Berg, 1985).
To delineate the behavioral algorithm underlying thermal navigation
in fish requires to observe behavior at high resolution in many in­
dividuals while precisely controlling the stimuli available to the animal.
Larval zebrafish readily navigate heat gradients in the laboratory (Gau
et al., 2013; Haesemeyer et al., 2015; Robson, 2013) and behavioral
experiments can be performed with high enough throughput to obtain
quantitative measures of behavior (Fig. 1B–C). Furthermore, larval
zebrafish swim in discrete bouts (Budick and O’Malley, 2000) which
greatly aids in the analysis of behavioral strategies, as each initiation of a
swim bout can be viewed as a separate behavioral decision (Johnson
et al., 2020; Marques et al., 2018). Behavioral quantification during
gradient navigation revealed that larval zebrafish utilize two major
behavioral strategies during thermal navigation. They will increase their
swim vigor the further they are from their preferred temperature, both
3
Molecular and Cellular Endocrinology 518 (2020) 110986
by increasing the frequency of swim bout initiation and the speed of
individual swim bouts. Furthermore, larval zebrafish increase the fre­
quency of turning when the change of temperature experienced during
the last swim is unfavorable (Fig. 1D) (Haesemeyer et al., 2015, 2019;
Robson, 2013). While increases in turning aren’t directional with
respect to the gradient, larval zebrafish tend to string together swims of
the same turn direction (Dunn et al., 2016) thereby allowing trajectory
reversals which aides heat gradient navigation (Robson, 2013). Notably,
the observed behavioral rules can be used to simulate behavior. Such
simulations approximate true gradient navigation to a large degree,
indicating that these rules are sufficient to explain the observed re­
striction to preferred temperatures (Robson, 2013).
How do larval zebrafish process temperature stimuli in order to enact
these behavioral rules of gradient navigation? To address this question,
we adopted a classical neuroscience paradigm, in which randomly
fluctuating stimuli are used to map the ideal stimulus driving a neuron,
to a behavioral task. Using a precisely targeted laser beam following a
freely swimming larval zebrafish allowed delivering such randomly
fluctuating temperature stimuli while recording behavioral responses.
This paradigm revealed that larval zebrafish integrate thermal infor­
mation in a time window of 500 ms preceding a swim bout. Further­
more, analyzing the ideal stimulus driving swim bouts demonstrated
that larval zebrafish behavior is both driven by absolute temperature
and the rate of change of temperature within this short time window, in
line with the observed behavioral strategy (Haesemeyer et al., 2015).
Intriguingly, while the ideal stimulus was largely similar across different
behaviors such as straight swims and turns, comparing it across behavior
types indicated that rapid temperature decreases towards the preferred
temperature led to fast straight movements (Haesemeyer et al., 2015).
This effect favors staying the course when moving in the direction of
favorable temperature changes as predicted based on simulations for
general fish temperature navigation (Neill, 1979). This difference in
processing likely also underlies the modulation of turning based on
swimming direction within the temperature gradient (Robson, 2013).
Behavioral thermoregulatory strategies are present across animal
phyla as well as in bacteria (Paster and Ryu, 2008). A shared element in
all these navigational strategies is the modulation of turning based on
whether the animal is moving towards or away from the preferred
temperature. C. elegans will lengthen straight runs when moving toward
the preferred temperature and shorten runs, thereby increasing turning,
when moving away (Ryu and Samuel, 2002). Unlike fish, when
C. elegans are close to the preferred temperature, they will engage in a
precise isothermal tracking behavior, effectively moving along a line of
near equal temperature (Hedgecock and Russell, 1975). Both adult
(Sayeed and Benzer, 1996) and larval Drosophila (Luo et al., 2010)
navigate temperature gradients. Much like C. elegans, Drosophila
modulate run durations based on whether they are moving away or
towards the preferred temperature (Luo et al., 2010). However, while
turn direction at the termination of a run is random in C. elegans,
Drosophila larvae will sample the gradient using headsweeps at the end
of a run and subsequently bias the turn in a favorable direction (Luo
et al., 2010). As in zebrafish, behavioral decisions in C. elegans and
Drosophila larvae rely on temporal integration of heat stimuli (Klein
et al., 2015; Ryu and Samuel, 2002).
To enact these behavioral strategies, fish and other animals need to
sense environmental temperature, represent this information in the
brain and ultimately transform the sensory information into appropriate
behaviors.
2.3. The thermosensory system
Across vertebrates, environmental temperature is sensed by neurons
of the trigeminal (Fig. 2A) and dorsal root ganglia that innervate the
facial skin and the skin of the trunk and tail, respectively (Butler and
Hodos, 2005). There is also strong evidence that at least some of the
molecules, namely thermo Trp (transient receptor potential) channels
M. Haesemeyer
(Jordt et al., 2003), involved in temperature sensation are even more
ancient and shared across divergent phyla. Their individual role how­
ever varies widely across species.
In Drosophila, TrpA1 functions as a heat sensor and is required for
thermotaxis behavior (Rosenzweig et al., 2005). Similarly, in pit vipers
TrpA1 is required for the detection of infrared radiation (Gracheva et al.,
2010). In mammals, the role of TrpA1 is controversial. While TrpA1 has
been reported as a sensor of cold and noxious cold (Bandell et al., 2004;
Story et al., 2003), recent evidence suggests that it does not play a role in
thermosensation but rather in chemosensation, most notably the
detection of mustard oil (Bautista et al., 2006; Knowlton et al., 2010).
Furthermore, ablating TrpA1 expressing neurons in mice does not affect
cold avoidance (Pogorzala et al., 2013). In zebrafish, TrpA1 is not sen­
sitive to temperature at all but also exclusively functions as a chemo­
sensor (Prober et al., 2008). The medaka TrpA1 homolog, on the other
hand, activates upon heating like the Drosophila variant (Oda et al.,
2017). The TrpV1 channel is generally heat sensitive across species
(Fig. 2B). In vitro, mammalian TrpV1 activates at temperatures above
40 ◦ C (Jordt et al., 2003). Zebrafish TrpV1 starts to activate at slightly
lower temperatures, covering a temperature range between 25 and 42 ◦ C
(Gau et al., 2013). However, the role of TrpV1 in vivo is less well
established and at least in mice it might be involved in sensing innoc­
uous rather than noxious heat similar to the zebrafish activation range
(Yarmolinsky et al., 2016). Furthermore, while ablation of TrpV1
expressing neurons leads to profound deficits in heat responses in mice
(Pogorzala et al., 2013), knockouts of the TrpV1 gene have only modest
effects (Caterina et al., 2000; Yarmolinsky et al., 2016). Similarly in
zebrafish, morpholino mediated knockdown of TrpV1 impairs but does
not abolish heat avoidance (Gau et al., 2013). This suggests that the
neurons expressing TrpV1 might be an important substrate in temper­
ature sensation but that there is a redundancy in receptors. Interestingly,
4
Molecular and Cellular Endocrinology 518 (2020) 110986
Fig. 2. Temperature sensation and process­
ing. A: Neurons of the trigeminal ganglion,
situated between the eye and the ear in
vertebrates, detect skin temperature across
the face. B: TrpV1 is one member of the
thermo-Trp family that gets activated by
higher temperatures. It passes cations when
activated, and thereby depolarizes the sen­
sory neuron. C: Schematic of the tempera­
ture processing circuit identified in larval
zebrafish (note, the brain shown is that of an
adult zebrafish). Environmental temperature
is detected by trigeminal (and dorsal root)
ganglia neurons which are exclusively
responding to temperature level. Local cir­
cuits in the hindbrain subsequently extract
the rate of temperature change and ulti­
mately control behavior generation.
so far no cold receptor has been identified in fish. The cold receptor
TrpM8 which is present in mammals, birds and amphibians is absent
from fish genomes (Gracheva and Bagriantsev, 2015; Kastenhuber et al.,
2013; Xu et al., 2014).
In zebrafish, the responses of trigeminal neurons to temperature
stimuli have been studied. TrpV1 expressing neurons respond to
warming in vivo (Gau et al., 2013) and overall temperature stimuli seem
to be encoded in two distinct functional classes of cells in the caudal part
of the trigeminal ganglion (Haesemeyer et al., 2018). Here, one class of
cells gets activated by warmth, potentially corresponding to the TrpV1
expressing population, while another population is activated by cold or
inhibited by warmth. In both these functional classes, activity encodes
the current temperature level (Haesemeyer et al., 2018). Since behav­
ioral studies have shown that larval zebrafish use information both
about the temperature level and the rate of change (Haesemeyer et al.,
2015), this raises the question of how the sensed environmental tem­
perature is processed by downstream circuits.
2.4. Central circuits and behavior generation
After environmental temperature is detected in sensory neurons, the
brain needs to process this information in order to generate adaptive
behaviors such as heat gradient navigation or shivering thermogenesis.
In general, little is known about central circuits processing temperature.
However, in mammals different brain regions have been implicated in
temperature processing (Solinski and Hoon, 2019). This includes the
preoptic hypothalamus for autonomous body temperature regulation as
well as brainstem and thalamic regions that control behavioral programs
while the cortex seems to be dispensable for thermoregulation (Yahiro
et al., 2017). In the common carp an fMRI study delineated a sensori­
motor pathway that controls escape in response to rapid cooling stimuli.
M. Haesemeyer
This pathway involves the trigeminal nerve as well as the cerebellum
(Van den Burg et al., 2006). However, while very useful to implicate
brain regions, the resolution of fMRI precludes a cellular level
understanding.
Larval zebrafish, due to its transparency and small size, allows
cellular resolution functional imaging of the entire brain. This approach
not only allows to implicate brain regions in thermosensation but can
identify different functional cell classes. Importantly, while many brain
regions might have cells responding to a given stimulus, having access to
all cells allows inferring the most likely flow of information through the
brain. Combining functional calcium imaging with heat stimuli and
behavioral recording in larval zebrafish allowed to delineate how in­
formation is processed in the brain during thermoregulatory behaviors
(Haesemeyer et al., 2018). Temperature sensitive cells in the caudal
domain of the trigeminal ganglion encode environmental temperature in
two channels: One ON channel that is activated by warmth and one OFF
channel that is inhibited. Circuits in the lateral hindbrain subsequently
extract information about the rate of change of temperature by effec­
tively differentiating the trigeminal inputs (Fig. 2C). Here, one new cell
type encodes the rate of temperature increase while another cell type is
activated as the temperature is decreasing. This information is then used
by hindbrain pre-motor cells that drive behavior such as swimming and
turning. In other words, as predicted by behavioral studies, larval
zebrafish has access to information about the rate of temperature
change, which in this case is extracted by circuits in the hindbrain
(Haesemeyer et al., 2015, 2018). Having access to cellular level infor­
mation together with behavior allowed to generate a circuit model of
temperature processing that can successfully predict neuronal activity
and behavior in response to novel stimuli (Haesemeyer et al., 2018).
Such cellular level realistic circuit models have the advantage that they
make testable predictions about circuit architecture which can be used
to design targeted future experiments. Namely, the precise biophysical
mechanism of how hindbrain neurons compute the rate of temperature
change from trigeminal inputs is still unknown, requiring further study.
Temperature processing in both mouse and Drosophila shares a
splitting into heat and cold activated channels with zebrafish (Frank
et al., 2015; Gallio et al., 2011; Liu et al., 2015; Ran et al., 2016). In
zebrafish specifically, these responses act in concert to control behavior,
such that heat and cold activated sensory neurons form separate ON and
OFF channels with overlapping temperature responses (Haesemeyer
et al., 2018). Such a feature of splitting information into ON and OFF
channels is widespread across sensory modalities and a similar over­
lapping mode of warmth detection has recently been confirmed in
mouse thermosensation (Paricio-Montesinos et al., 2020). In the mouse
trigeminal ganglion, sensory neurons tile temperature space with
different neurons activating at different temperatures (Yarmolinsky
et al., 2016). Presumed second order neurons in the spinal cord display a
coding strategy whereby warmth activated neurons largely encode the
temperature level while another class of cells specifically responds to
decreases in temperature (Ran et al., 2016). Second order temperature
neurons in Drosophila encode temperature level or rate of change in both
ON and OFF channels similar to zebrafish hindbrain cells (Frank et al.,
2015; Liu et al., 2015). However, while there are no cells in zebrafish
that respond to both warming and cooling such cells with broader
specificity have been found in Drosophila (Frank et al., 2015; Liu et al.,
2015). Furthermore, while sensory neurons in zebrafish exclusively
encode the temperature level, some Drosophila sensory neurons already
specifically encode heating or cooling instead of warmth and cold
(Budelli et al., 2019). This is similar to the C. elegans AFD sensory neuron
which encodes a mixture of warmth and warming (Clark et al., 2006,
2007; Mori and Ohshima, 1995). This argues for both conservation in
the representation of temperature in the brain across species as well as
species specific adaptations.
However, aside from the hindbrain circuits that likely control
behavior, temperature is represented in many brain regions in zebrafish
on diverse time scales. This includes forebrain regions and the preoptic
5
Molecular and Cellular Endocrinology 518 (2020) 110986
hypothalamus which plays a key role in temperature regulation in
mammals (Haesemeyer et al., 2018; Nakamura, 2011). Temperature
encoding in these brain regions might serve higher order processes such
as learning. Through operant conditioning goldfish can learn to control
the water temperature in their bowl using lever presses (Rozin and
Mayer, 1961) and larval zebrafish can bias tail flick direction to turn off
a noxious heat stimulus (Lin et al., 2019). Such tasks may well rely on
temperature processing in different brain regions. Furthermore, tem­
perature preference is not absolute but modulated by internal state and
other environmental factors. Therefore, heat encoding cells in other
brain regions might be important for setpoint changes and behavioral
flexibility.
2.5. Regulation of thermal responses
Just as metabolic needs can change, temperature preferences in an­
imals are often flexible and can vary dependent on internal state as well
as environmental contingencies (Fig. 3). Upon infection, pyrogenic
messengers induce fever in mammals during which the core body tem­
perature is elevated. A critical mediator of this pathway is the preoptic
area of the hypothalamus which integrates information about external
and internal body temperature (Liedtke, 2017; Nakamura, 2011).
However, fever responses are not limited to endotherms, but many
ectotherm species including fish employ behavioral means to raise their
body temperature upon infection (Boltana et al., 2013; Casterlin and
Reynolds, 1977; Reynolds and Casterlin, 1979). And our own experience
as well as experimental evidence tells us that fever responses also
include a behavioral component in mammals (Crawshaw and Stitt,
1975). Intriguingly, the zebrafish preoptic area contains temperature
encoding cells (Haesemeyer et al., 2018) which may indicate a conser­
vation of pathways involved in modulating preferred body temperature.
Changes in temperature preference on short timescales are observed
in the sculpin. After feeding, juvenile sculpin seek out warmer
Fig. 3. Control of temperature preference by internal states and environmental
factors. On an abstract level, thermoregulation can be compared to an engi­
neered thermostat controlling the temperature of an apartment. As in a ther­
mostat, larval zebrafish presumably compare (Blue triangle) current
temperature conditions (Thermometer) with an internal desired setpoint (Dial)
to control thermoregulatory behaviors. The generated behavior on the other
hand will move the fish to a different place and thereby feeds back on the
temperature experience (Bottom arrow). Work across fish species indicates that
different environmental and internal conditions influence the desired temper­
ature setpoint, effectively “turning the dial” of the thermostat to a new
desired setting.
M. Haesemeyer
temperatures by vertically migrating towards the surface. Here, water is
on average 10 ◦ C warmer than at the bottom. This migration to warmer
water in fact significantly enhances digestion and growth rates in
sculpin indicating an adaptive link between feeding state and thermo­
regulatory behavior (Wurtsbaugh and Neverman, 1988). Such feeding
state dependent changes in preferred temperature are not limited to the
sculpin but are also observed in other fish (Reynolds and Casterlin,
1979) indicating a general synchronization between metabolic need and
thermoregulation.
Hypoxic conditions tend to reduce the preferred temperature in fish
(Schurmann et al., 1991; Petersen and Steffensen, 2003; Schurmann and
Steffensen, 1992, 1994; Schurmann et al., 1991). This is adaptive since
the metabolism and therefore oxygen need decreases at lower temper­
atures. At the same time, the higher oxygen solubility in cold water
means that oxygen exchange via the gills becomes more efficient at
lower temperatures (Schurmann et al., 1991). In a temperature gradient
it is expected that cooler areas of the gradient will have more dissolved
oxygen than warmer zones. While this is likely adding to the adaptive
potential of lowering the temperature preference it obfuscates whether
fish navigate a thermal or an oxygen gradient. However, even when fish
can control the temperature in a tank system without the presence of a
gradient under constant hypoxic conditions they will still seek out a
lower preferred temperature (Schurmann et al., 1991). This argues that
there is a true interaction between sensing hypoxic conditions and
lowering preferred temperature.
How might these different setpoint changes be regulated? Different
peptidergic cell populations in the zebrafish hypothalamus are impli­
cated in heat avoidance behavior (Lovett-Barron et al., 2020; Madelaine
et al., 2017) and overexpression of specific peptides such as cart and cgrp
enhance behavioral temperature responses (Woods et al., 2014). This
hints at an endocrine regulation of thermoregulatory behaviors which
could influence the temperature fish ultimately seek out in a heat
gradient. Such a regulation could for example occur by peptidergic
modulation of synaptic gain in the hindbrain circuits that control ther­
moregulatory behavior such as the heat circuit identified in larval
zebrafish.
3. Outlook
Thermoregulation is clearly important to fish and they display
thermoregulatory behavior such as heat gradient navigation in order to
reach their optimal body temperature. Circuits controlling these be­
haviors are beginning to be unraveled in the larval zebrafish model
system. However, much could be learned from comparative studies
given the vast differences in preferred temperatures between fish. At this
point it is entirely unclear where these differences in temperature
preference arise: Are receptor proteins tuned to different temperature
ranges while the rest of the processing circuit is largely conserved? Or
are the receptor proteins responding in a similar manner to environ­
mental temperature but the encoding of thermo-channel opening into
sensory neuron activity is different? Or does the difference in thermal
preference arise due to differences in central processing such as changes
in how the activity of hindbrain temperature encoding neurons in­
fluences pre-motor neurons? Due to modern day cellular molecular
techniques including vastly reduced costs in genome sequencing, dif­
ferences in molecular composition or sensory physiology could likely be
answered in in vitro systems. Differences in central processing are
considerably harder to address in non-model systems. However, some
comparison species like medaka or Danionella translucida are being
established as neuroscience model systems and could be tested for their
thermal preference (Cook et al., 2018; Oda et al., 2017; Schulze et al.,
2018). Since medaka is often found in cooler habitats with temperatures
around 20 ◦ C (Fukuda, 2009) it could be a useful model for comparative
neuroethology in thermoregulation. Furthermore, models developed for
larval zebrafish thermosensation as well as artificial neural network
comparison models that make clear predictions about the logic of
6
Molecular and Cellular Endocrinology 518 (2020) 110986
temperature processing may be used to suggest targeted experiments to
study thermoregulation (Haesemeyer et al., 2018, 2019). This would
reduce the experimental burden and might therefore increase feasibility
of testing central processing across species.
Beyond modeling studies, developmental adaptations within species
can give important insight into how circuits could potentially adapt to
different thermal habitats. When Xenopus tadpoles are grown at cold
temperatures, activation of TrpM8 channels in the spinal cord leads to
an increase in spontaneous motor neuron activity. This activity increase
ultimately results in a larger motor neuron pool through a reduction in
apoptosis (Spencer et al., 2019). This adaptation allows the tadpoles to
readily perform escape maneuvers at lower temperature. This suggests
that sensitization through increases in the number of circuit elements
could form an important part of behavioral adaptations across species as
well.
Another fruitful future research avenue is to try and understand the
interaction of internal states and temperature preference. Based on
behavioral observations discussed above this includes questions as to
how hypoxic conditions are sensed by fish and how states of hypoxia,
infection and satiation are integrated with the thermosensory system to
bring about changes in preferred temperature.
Conflicts of interest
The author declares that no competing interests exist.
Acknowledgements
I thank The Ohio State University Wexner Medical Center for funding
and the anonymous reviewers for comments and suggestions on the
manuscript.
References
Alt, W., 1980. Biased random walk models for chemotaxis and related diffusion
approximations. J. Math. Biol. 9, 147–177.
Bandell, M., Story, G.M., Hwang, S.W., Viswanath, V., Eid, S.R., Petrus, M.J., Earley, T.J.,
Patapoutian, A., 2004. Noxious cold ion channel TRPA1 is activated by pungent
compounds and bradykinin. Neuron 41, 849–857.
Bautista, D.M., Jordt, S.-E., Nikai, T., Tsuruda, P.R., Read, A.J., Poblete, J., Yamoah, E.N.,
Basbaum, A.I., Julius, D., 2006. TRPA1 mediates the inflammatory actions of
environmental irritants and proalgesic agents. Cell 124, 1269–1282.
Beitinger, T.L., Fitzpatrick, L.C., 1979. Physiological and ecological correlates of
preferred temperature in fish. Integr. Comp. Biol. 19, 319–329.
Berg, H.C., 1985. Physics of bacterial chemotaxis. In: Sensory Perception and
Transduction in Aneural Organisms. Springer US), pp. 19–30.
Boltana, S., Rey, S., Roher, N., Vargas, R., Huerta, M., Huntingford, F.A., Goetz, F.W.,
Moore, J., Garcia-Valtanen, P., Estepa, A., et al., 2013. Behavioural fever is a
synergic signal amplifying the innate immune response. Proc. Biol. Sci. 280,
20131381.
Booker, D.J., Wells, N.C., Smith, I.P., 2008. Modelling the trajectories of migrating
Atlantic salmon (Salmo salar). Can. J. Fish. Aquat. Sci. 65, 352–361.
Brix, O., Forås, E., Strand, I., 1998. Genetic variation and functional properties of
Atlantic cod hemoglobins: introducing a modified tonometric method for studying
fragile hemoglobins. Comp. Biochem. Physiol. Mol. Integr. Physiol. 119, 575–583.
Budelli, G., Ni, L., Berciu, C., van Giesen, L., Knecht, Z.A., Chang, E.C., Kaminski, B.,
Silbering, A.F., Samuel, A., Klein, M., et al., 2019. Ionotropic receptors specify the
morphogenesis of phasic sensors controlling rapid thermal preference in Drosophila.
Neuron 101, 738–747 e3.
Budick, S.A., O’Malley, D.M., 2000. Locomotor repertoire of the larval zebrafish:
swimming, turning and prey capture. J. Exp. Biol. 203, 2565–2579.
Butler, A.B., Hodos, W., 2005. Comparative Vertebrate Neuroanatomy: Evolution and
Adaptation. John Wiley & Sons.
Byron, C.J., Burke, B.J., 2014. Salmon ocean migration models suggest a variety of
population-specific strategies. Rev. Fish Biol. Fish. 24, 737–756.
Carey, F.G., Teal, J.M., Kanwisher, J.W., Lawson, K.D., Beckett, J.S., 1971. Warm-bodied
fish. Integr. Comp. Biol. 11, 137–143.
Casterlin, M.E., Reynolds, W.W., 1977. Behavioral fever in anuran amphibian larvae. Life
Sci. 20, 593–596.
Caterina, M.J., Leffler, A., Malmberg, A.B., Martin, W.J., Trafton, J., Petersen-Zeitz, K.R.,
Koltzenburg, M., Basbaum, A.I., Julius, D., 2000. Impaired nociception and pain
sensation in mice lacking the capsaicin receptor. Science 288, 306–313.
Clark, D.A., Biron, D., Sengupta, P., Samuel, A.D.T., 2006. The AFD sensory neurons
encode multiple functions underlying thermotactic behavior in Caenorhabditis
elegans. J. Neurosci. 26, 7444–7451.
M. Haesemeyer
Clark, D.A., Gabel, C.V., Gabel, H., Samuel, A.D.T., 2007. Temporal activity patterns in
thermosensory neurons of freely moving Caenorhabditis elegans encode spatial
thermal gradients. J. Neurosci. 27, 6083–6090.
Cook, E.S.B., Barrios, J.P., Bertram, E.P.L., Douglass, A.D., 2018. Establishment of the
Miniature Fish Species Danionella Translucida as a Genetically and Optically
Tractable Neuroscience Model.
Coutant, C.C., 1977. Compilation of temperature preference data. J. Fish. Res. Board
Can. 34, 739–745.
Crawshaw, L.I., Stitt, J.T., 1975. Behavioural and autonomic induction of prostaglandin
E-1 fever in squirrel monkeys. J. Physiol. 244, 197–206.
Cully, M., 2019. Zebrafish earn their drug discovery stripes. Nat. Rev. Drug Discov. 18,
811–813.
Dunn, T.W., Mu, Y., Narayan, S., Randlett, O., Naumann, E.A., Yang, C.-T., Schier, A.F.,
Freeman, J., Engert, F., Ahrens, M.B., 2016. Brain-wide mapping of neural activity
controlling zebrafish exploratory locomotion. Elife 5, e12741.
Engeszer, R.E., Patterson, L.B., Rao, A.A., Parichy, D.M., 2007. Zebrafish in the wild: a
review of natural history and new notes from the field. Zebrafish 4, 21–40.
Fraenkel, G.S., Gunn, D.L., 1961. The Orientation of Animals: Kineses, Taxes and
Compass Reactions. Dover, New York, USA.
Frank, D.D., Jouandet, G.C., Kearney, P.J., Macpherson, L.J., Gallio, M., 2015.
Temperature representation in the Drosophila brain. Nature 519, 358–361.
Fukuda, S., 2009. Consideration of fuzziness: is it necessary in modelling fish habitat
preference of Japanese medaka (Oryzias latipes)? Ecol. Model. 220, 2877–2884.
Gallio, M., Ofstad, T.A., Macpherson, L.J., Wang, J.W., Zuker, C.S., 2011. The coding of
temperature in the Drosophila brain. Cell 144, 614–624.
Gammon, J.R., 1998. The Wabash River Ecosystem. Indiana University Press.
Gau, P., Poon, J., Ufret-Vincenty, C., Snelson, C.D., Gordon, S.E., Raible, D.W., Dhaka, A.,
2013. The zebrafish ortholog of TRPV1 is required for heat-induced locomotion.
J. Neurosci. 33, 5249–5260.
Goyer, K., Bertolo, A., Pépino, M., Magnan, P., 2014. Effects of lake warming on
behavioural thermoregulatory tactics in a cold-water stenothermic fish. PLoS One 9,
e92514.
Gracheva, E.O., Bagriantsev, S.N., 2015. Evolutionary adaptation to thermosensation.
Curr. Opin. Neurobiol. 34, 67–73.
Gracheva, E.O., Ingolia, N.T., Kelly, Y.M., Cordero-Morales, J.F., Hollopeter, G.,
Chesler, A.T., Sánchez, E.E., Perez, J.C., Weissman, J.S., Julius, D., 2010. Molecular
basis of infrared detection by snakes. Nature 464, 1006–1011.
Haesemeyer, M., Robson, D.N., Li, J.M., Schier, A.F., Engert, F., 2015. The structure and
timescales of heat perception in larval zebrafish. Cell Syst 1, 338–348.
Haesemeyer, M., Robson, D.N., Li, J.M., Schier, A.F., Engert, F., 2018. A brain-wide
circuit model of heat-evoked swimming behavior in larval zebrafish. Neuron 98,
817–831 e6.
Haesemeyer, M., Schier, A.F., Engert, F., 2019. Convergent temperature representations
in artificial and biological neural networks. Neuron 103, 1123–1134 e6.
Hedgecock, E.M., Russell, R.L., 1975. Normal and mutant thermotaxis in the nematode
Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 72, 4061–4065.
Ivlev, V.S., 1960. Analysis of the mechanism of distribution of fishes under the conditions
of a temperature gradient. Zool. Zhurnal 39, 494–499.
Johnson, R.E., Linderman, S., Panier, T., Wee, C.L., Song, E., Herrera, K.J., Miller, A.,
Engert, F., 2020. Probabilistic models of larval zebrafish behavior reveal structure on
many scales. Curr. Biol. 30, 70–82.e4.
Jordt, S.-E., McKemy, D.D., Julius, D., 2003. Lessons from peppers and peppermint: the
molecular logic of thermosensation. Curr. Opin. Neurobiol. 13, 487–492.
Karpov, A.K., Novikov, G.G., 1980. Hemoglobin alloforms in cod, Gadus morhua
(Gadiformes, Gadidae), their functional characteristics and occurrence in
populations. J. Ichthyol. 20, 45–50.
Kastenhuber, E., Gesemann, M., Mickoleit, M., Neuhauss, S.C.F., 2013. Phylogenetic
analysis and expression of zebrafish transient receptor potential melastatin family
genes. Dev. Dynam. 242, 1236–1249.
Kennedy, V.S., Mihursky, J., 1967. Bibliography on the Effects of Temperature in the
Aquatic Environment. Natural Resources Institute, University of Maryland.
Kessler, A.R., 2002. Tourette syndrome associated with body temperature dysregulation:
possible involvement of an idiopathic hypothalamic disorder. J. Child Neurol. 17,
738–744.
Klein, M., Afonso, B., Vonner, A.J., Hernandez-Nunez, L., Berck, M., Tabone, C.J.,
Kane, E.A., Pieribone, V.A., Nitabach, M.N., Cardona, A., et al., 2015. Sensory
determinants of behavioral dynamics in Drosophila thermotaxis. Proc. Natl. Acad.
Sci. U.S.A. 112, E220–E229.
Knowlton, W.M., Bifolck-Fisher, A., Bautista, D.M., McKemy, D.D., 2010. TRPM8, but not
TRPA1, is required for neural and behavioral responses to acute noxious cold
temperatures and cold-mimetics in vivo. Pain 150, 340–350.
Liedtke, W.B., 2017. Deconstructing mammalian thermoregulation. Proc. Natl. Acad. Sci.
U.S.A. 114, 1765–1767.
Lin, Q., Helmreich, M., Schlumm, F., Li, J.M., Robson, D.N., Engert, F., Schier, A.,
Nöbauer, T., Vaziri, A., 2019. Cerebellar Neurodynamics during Motor Planning
Predict Decision Timing and Outcome on Single-Trial Level.
Liu, W.W., Mazor, O., Wilson, R.I., 2015. Thermosensory processing in the Drosophila
brain. Nature 519, 353–357.
Löffler, S., Danos, P., Schillen, T.B., Klimke, A., 2008. Recurrent dysregulation of body
temperature during antipsychotic pharmacotherapy. Psychiatr. Prax. 35, 91–93.
Lovett-Barron, M., Chen, R., Bradbury, S., Andalman, A.S., Wagle, M., Guo, S.,
Deisseroth, K., 2020. Multiple convergent hypothalamus–brainstem circuits drive
defensive behavior. Nat. Neurosci. 23 (8), 959–967. https://doi.org/10.1038/
s41593-020-0655-1.
7
Molecular and Cellular Endocrinology 518 (2020) 110986
Luo, L., Gershow, M., Rosenzweig, M., Kang, K., Fang-Yen, C., Garrity, P.A., Samuel, A.D.
T., 2010. Navigational decision making in Drosophila thermotaxis. J. Neurosci. 30,
4261–4272.
Madelaine, R., Lovett-Barron, M., Halluin, C., Andalman, A.S., Liang, J., Skariah, G.M.,
Leung, L.C., Burns, V.M., Mourrain, P., 2017. The hypothalamic NPVF circuit
modulates ventral raphe activity during nociception. Sci. Rep. 7, 41528.
Marques, J.C., Lackner, S., Félix, R., Orger, M.B., 2018. Structure of the zebrafish
locomotor repertoire revealed with unsupervised behavioral clustering. Curr. Biol.
28, 181–195 e5.
Mori, I., Ohshima, Y., 1995. Neural regulation of thermotaxis in Caenorhabditis elegans.
Nature 376, 344–348.
Nakamura, K., 2011. Central circuitries for body temperature regulation and fever. Am.
J. Physiol. Regul. Integr. Comp. Physiol. 301, R1207–R1228.
Neill, W.H., 1979. Mechanisms of fish distribution in heterothermal environments.
Integr. Comp. Biol. 19, 305–317.
Neill, W.H., Magnuson, J.J., 1974. Distributional ecology and behavioral
thermoregulation of fishes in relation to heated effluent from a power plant at Lake
Monona, Wisconsin. Trans. Am. Fish. Soc. 103, 663–710.
Neill, W.H., Magnuson, J.J., Chipman, G.G., 1972. Behavioral thermoregulation by
fishes: a new experimental approach. Science 176, 1443–1445.
Oda, M., Saito, K., Hatta, S., Kubo, Y., Saitoh, O., 2017. Chemical and thermal sensitivity
of medaka TRPA1 analyzed in heterologous expression system. Biochem. Biophys.
Res. Commun. 494, 194–201.
Ohlberger, J., Mehner, T., Staaks, G., Hölker, F., 2008. Temperature-related
physiological adaptations promote ecological divergence in a sympatric species pair
of temperate freshwater fish. Coregonus spp. Funct. Ecol. 22, 501–508.
Paricio-Montesinos, R., Schwaller, F., Udhayachandran, A., Rau, F., Walcher, J.,
Evangelista, R., Vriens, J., Voets, T., Poulet, J.F.A., Lewin, G.R., 2020. The sensory
coding of warm perception. Neuron 106 (105), 830–841.e3. https://doi.org/
10.1016/j.neuron.2020.02.035.
Paster, E., Ryu, W.S., 2008. The thermal impulse response of Escherichia coli. Proc. Natl.
Acad. Sci. U.S.A. 105, 5373–5377.
Petersen, M.F., Steffensen, J.F., 2003. Preferred temperature of juvenile Atlantic cod
Gadus morhua with different haemoglobin genotypes at normoxia and moderate
hypoxia. J. Exp. Biol. 206, 359–364.
Pogorzala, L.A., Mishra, S.K., Hoon, M.A., 2013. The cellular code for mammalian
thermosensation. J. Neurosci. 33, 5533–5541.
Prober, D.A., Zimmerman, S., Myers, B.R., McDermott Jr., B.M., Kim, S.-H., Caron, S.,
Rihel, J., Solnica-Krezel, L., Julius, D., Hudspeth, A.J., et al., 2008. Zebrafish TRPA1
channels are required for chemosensation but not for thermosensation or
mechanosensory hair cell function. J. Neurosci. 28, 10102–10110.
Rakus, K., Ronsmans, M., Vanderplasschen, A., 2017. Behavioral fever in ectothermic
vertebrates. Dev. Comp. Immunol. 66, 84–91.
Ran, C., Hoon, M.A., Chen, X., 2016. The coding of cutaneous temperature in the spinal
cord. Nat. Neurosci. 19, 1201–1209.
Refinetti, R., 1999. Amplitude of the daily rhythm of body temperature in eleven
mammalian species. J. Therm. Biol. 24, 477–481.
Reynolds, W.W., Casterlin, M.E., 1979. Behavioral thermoregulation and the “final
preferendum” paradigm. Am. Zool. 19, 211–224.
Robson, D.N., 2013. Thermal Navigation in Larval Zebrafish. Doctoral dissertation.
Harvard University. http://nrs.harvard.edu/urn-3:HUL.InstRepos:11158267.
Roger, P.A., 1996. Biology and Management of the Floodwater Ecosystem in Rice Fields.
Int. Rice Res. Inst.
Rose, G.A., Leggett, W.C., 1988. Atmosphere–ocean coupling and atlantic cod
migrations: effect of wind-forced variations in sea temperatures and currents or
nearshore distributions and catch rates of Gadus morhua. Can. J. Fish. Aquat. Sci. 45,
1234–1243.
Rosenzweig, M., Brennan, K.M., Tayler, T.D., Phelps, P.O., Patapoutian, A., Garrity, P.A.,
2005. The Drosophila ortholog of vertebrate TRPA1 regulates thermotaxis. Genes
Dev. 19, 419–424.
Rozin, P.N., Mayer, J., 1961. Thermal reinforcement and thermoregulatory behavior in
the goldfish, Carassius auratus. Science 134, 942–943.
Ryu, W.S., Samuel, A.D.T., 2002. Thermotaxis in Caenorhabditis elegans analyzed by
measuring responses to defined Thermal stimuli. J. Neurosci. 22, 5727–5733.
Sayeed, O., Benzer, S., 1996. Behavioral genetics of thermosensation and hygrosensation
in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 93, 6079–6084.
Schulze, L., Henninger, J., Kadobianskyi, M., Chaigne, T., Faustino, A.I., Hakiy, N.,
Albadri, S., Schuelke, M., Maler, L., Del Bene, F., et al., 2018. Transparent Danionella
translucida as a genetically tractable vertebrate brain model. Nat. Methods 15,
977–983.
Schurmann, H., Steffensen, J., 1994. Spontaneous swimming activity OF atlantic cod
GADUS morhua exposed to graded hypoxia at three temperatures. J. Exp. Biol. 197,
129–142.
Schurmann, H., Steffensen, J.F., 1992. Lethal oxygen levels at different temperatures and
the preferred temperature during hypoxia of the Atlantic cod, Gadus morhua L.
J. Fish. Biol. 41, 927–934.
Schurmann, H., Steffensen, J.F., Lomholt, J.P., 1991. The influence of hypoxia on the
preferred temperature of rainbow trout Oncorhynchus mykiss. J. Exp. Biol. 157,
75–86.
Singer, H.S., 2010. Treatment of tics and tourette syndrome. Curr. Treat. Options Neurol.
12, 539–561.
Solinski, H.J., Hoon, M.A., 2019. Cells and circuits for thermosensation in mammals.
Neurosci. Lett. 690, 167–170.
Spencer, K.A., Belgacem, Y.H., Visina, O., Shim, S., Genus, H., Borodinsky, L.N., 2019.
Growth at cold temperature increases the number of motor neurons to optimize
locomotor function. Curr. Biol. 29, 1787–1799 e5.
M. Haesemeyer
Story, G.M., Peier, A.M., Reeve, A.J., Eid, S.R., Mosbacher, J., Hricik, T.R., Earley, T.J.,
Hergarden, A.C., Andersson, D.A., Hwang, S.W., et al., 2003. ANKTM1, a TRP-like
channel expressed in nociceptive neurons, is activated by cold temperatures. Cell
112, 819–829.
Sullivan, C.M., 1954. Temperature reception and responses in fish. J. Fish. Res. Board
Can. 11, 153–170.
Tan, C.L., Knight, Z.A., 2018. Regulation of body temperature by the nervous system.
Neuron 98, 31–48.
Van den Burg, E.H., Verhoye, M., Peeters, R.R., 2006. Activation of a sensorimotor
pathway in response to a water temperature drop in a teleost fish. J. Health.com 209
(Pt 11), 2015–2024. https://doi.org/10.1242/jeb.02240.
Woods, I.G., Schoppik, D., Shi, V.J., Zimmerman, S., Coleman, H.A., Greenwood, J.,
Soucy, E.R., Schier, A.F., 2014. Neuropeptidergic signaling partitions arousal
behaviors in zebrafish. J. Neurosci. 34, 3142–3160.
Molecular and Cellular Endocrinology 518 (2020) 110986
Wurtsbaugh, W.A., Neverman, D., 1988. Post-feeding thermotaxis and daily vertical
migration in a larval fish. Nature 333, 846–848.
Xu, P., Zhang, X., Wang, X., Li, J., Liu, G., Kuang, Y., Xu, J., Zheng, X., Ren, L., Wang, G.,
et al., 2014. Genome sequence and genetic diversity of the common carp, Cyprinus
carpio. Nat. Genet. 46, 1212–1219.
Yahiro, T., Kataoka, N., Nakamura, Y., Nakamura, K., 2017. The lateral parabrachial
nucleus, but not the thalamus, mediates thermosensory pathways for behavioural
thermoregulation. Sci. Rep. 7, 5031.
Yarmolinsky, D.A., Peng, Y., Pogorzala, L.A., Rutlin, M., Hoon, M.A., Zuker, C.S., 2016.
Coding and plasticity in the mammalian thermosensory system. Neuron 92,
1079–1092.