Part I
Thermoreception
1
Chapter 1
Cutaneous Thermoreception
Todd Everson; et al.
1.1
thermosensory systems provides a survival advantage. Once we have identified these important factors, we can identify how heat actually
elicits a response from the central nervous system, and get a glimpse of what some of those
responses are.
Introduction
The life of an organism depends on its ability to
coordinate numerous biochemical reactions and
respond to changes in its environment. Temperature change can influence many of these
chemical reactions and thus influence important
functions such as metabolism, oxygen transport,
and nerve function. So how does an organism
know when the temperature of the environment
has changed? What types of cells detect a
change in temperature that may be harmful
to the organism? How are the signals from
these cells integrated into usable information?
Why do extreme temperatures elicit a painful
response?
1.1.1
Physical
Heat
Properties
of
Temperature is defined as the average energy
of molecular motion. Motion and temperature
have a direct proportional relationship, so if
motion increases, so does temperature. When
looking at the big picture, temperature determines the direction of heat-flow. Heat flows
from high temperatures to lower temperatures
in an attempt to acheive a thermal equilibruim.
Thus, if a cell is placed in an environment that
is warmer than it is, the cell absorbs heat and
it’s overall temperature increases. If the cell
is placed in an environment cooler than it is,
the cell looses heat to the environment and it’s
temperature drops.
A basic understanding of heat and temperature is necessary before discussing biological activity that allows temperature sensation. Then
we can investigate how heat interacts with biological tissues, and why having a cutaneous
3
4
1.1.2
CHAPTER 1. CUTANEOUS THERMORECEPTION
Biological Interactions
discrimiative temperature sensation. Descriminitive temperature sense allows animals to
At extreme high temperatures, proteins will de- localize and characterize temperatures that are
nature and lose their functionality. At extreme in contact with the skin.
low temperatures, chemical reactions slow down
Many endothermic animals integrate the senor halt altogether. Thus, most animals main- sory information received from the periphery
tain a thermoneutral range, in which their bio- with the thermosensory information produced
logical processes function with the highest effi- in the internal organs. The combined informacacy. Without thermonsensors, species would tion is analyzed, and efferent signals are sent out
have difficulty maintaining homeostasis and to elicit physiological and behavioral responses.
avoiding tissue damage due to noxious tem- For example, a thermoregulatory response to
perature extremes [11]. Many animals use ther- heat induces vasodilation at the periphery and
moregulation, involving both behavioral and induces perspiration. However, it also affects
physiological mechanisms, to maintain their other systems that are not associated with thercore temperature within their thermonuetral moregulation, such as suppression of hunger,
range. Cutaneous thermoreceptors equip ani- increased thirst, and increased secretion of anmals with an effective sensory system for both tidiuretic hormone to increase water retention.
of the above purposes.
Thus our thermosensory system is an integral
In mammals, body temperature (TB ) is maintained at a temperature much closer to the
upper survival limit than it is to the lower survival limit. At this temperature, chemical processes function at ideal rates. However, minor
changes in temperature, if not corrected for,
can be very dangerous. For instance, an increase in TB by just a few degrees Celsius may
be life threatening, whereas a decrease in TB
by the same magnitude may just be uncomfortable [14]. Fittingly, the internal thermosensors
primarily are warm-sense neurons, and act as
a last line of defense against changes in temperature. The cutaneous thermoreceptors are
the first line of defense, and consist of both
warm- and cool- sense neurons. Also, the majority of internal thermoreceptors are involved
in homeostasis, whereas the peripheral thermoreceptors are split between homeostasis and
part not just in thermoregulation, but of the
entire homeostatic mechanism [10].
1.1.3
Evolutionary History
The ability to sense temperature shows a number of parallels between multicellular and unicellular organisms, which suggests the roots
of thermoreception are embeded deep in phylogeny. Even the Paramecium possesses ion
channels that are influenced by heating and
cooling. It also exhibits behavioral thermoregulatory responses when exposed to temperatures
outside its typical environmental range [4].
Many traits of vertebrates are evolutionarily conservative, however, one obvious divergence in evolutionary history is the development of both homeotherms and ectotherms.
1.1. INTRODUCTION
Homeotherms, such as humans, are animals
that regulate their body temperature, through
a number of physiological responses, within a
very small range. Ectotherms, such as snakes,
have evolved biochemical processes that can
function at considerably variable body temperatures [13]. Ectotherms have complex thermoregulatory behaviors, yet few have been shown to
express cutaneous thermoreceptors. Much of
their behavior is dependent on information from
deep thermoreceptors. However, some peripheral thermoreceptors have been identified in
crocodiles and some lizards.
5
in thermoreception are discussed in the TRP
section of this chapter.
After discovering that TRP ion channels are
necessary for thermoreception, research began
to focus on how the TRP channels trasduce
thermal information into action potentials. The
identification of temperature sensitive TRP ion
channels has also allowed for more effective
ways of identifying which nerves are involved
in thermoreception.
The last decade of research has shed new
light on the mechanisms of action for thermoreceptors. The prevailing theory ten years ago
focused on Na+ and K+ as the primary con1.1.4 Scientific History
tributers to depolarization. The theory was
based on the idea that at room temperature,
+
+
Thermoreception, along with all somatosensory the Na /K ATPase developes the cell’s negasystems received some very important informa- tive membrane potential:
tion in 1969. An experiment was performed on
Drosophila with sustained exposure to bright
• For cool-receptors: Warming accelerates
light. Some of the mutant Drosophila had phothe Na+ /K+ ATPase which hyperpolarizes
toreceptors that responded to the sustained
the membrane and causes cold receptors to
light with a transient receptor potential instead
decrease their firing rates. Cooling slows
of the expected plateau seen with most recepthe Na+ /K+ ATPase which allows the cold
tor activations. Thus, this type of receptor was
receptors to depolarize, producing an innamed a transient receptor potential (TRP) ion
creased firing rate [10].
channel [18].
• For warm-receptors: Warming has a
greater effect on passive Na+ current comIt took nearly two decades until this TRP
pared to K+ currents. Thus warming rereceptor was cloned, and finally in 1995 the first
sults in relatively more Na+ flowing in,
mammalian homolog of the Drosophila TRP
than K+ flowing out which depolarizes the
was discovered. Since this discovery, over 50
neuron and increases the firing rate [10].
TRP genes have been discovered in mammals,
worms, insects, fish and yeast. Seven subfamilies of TRP ion channels have been discovered
This theory has undergone some revisions
up to this point [18]. The subfamilies important over the last decade. Now it is recognized that
6
CHAPTER 1. CUTANEOUS THERMORECEPTION
Figure 1.1: Afferent Aδ fibers and C fibers embedded in the skin. The Aδ fibers are myelinated, and
are found at a depth of approxiamtely 150µm, near the interface between the dermis and the epidermis.
The C fibers unmyelinated, and are very superficial. The C fibers actually interdigitate between the
keratinocytes in the epidermis. Adapted from source 16
1.2. MECHANISMS OF THERMORECEPTION
the K+ channels and the Na+ /K+ ATPase exhibit non-normal activity at certain temperatures. However, these changes in ion concentration are likely secondary to the actual mechanisms. The current theory focuses on an influx
of Ca2+ as the ion most often responsible for
the production of action potentials.
1.2
Mechanisms of Thermoreception
7
in the epidermis. It has been demonstarted that
mice lacking the genes for these thermosensitive
ion channels have substantial defecits in their
ability to sense warm and noxious hot temperatures. Thus, keratinocytes may be secondory
sense cells, and the epidermis may be a large,
continuous thermosensory organ [18].
Cold-sense thermoreceptive neurons are
myelinated Aδ fibers 1.5 − 3µm in diameter.
Whereas heat-sense thermoreceptive neurons
are unmyelinated C fibers 1 − 2µm in diameter
(2). Since the axons of the Aδ fibers are myelinated, they transduce information via action
potentials far more rapidly than the unmyelinated C fibers. In fact, Aδ fibers have been
shown to transudce information at a velocity
as high as 19m/s, although typical human Aδ
fibers transduce action potentialss at approximately 9m/s. The C fibers typically transduce
action potentials at 0.8m/s [17].
Thermoreception, like other sensory systems, is
very complex. We will approach it from the big
picture first, looking at which nerves and organs are responsible for thermoreception. Then
we will learn about the signals transmitted to
the central nervous system, and how those signals are transmitted. Last will will earn about
the receptor proteins that elicit the nervous
response to temperature, and their mechanisms
The C fiber dendrites are more superficial
of action.
than the Aδ fiber dendrites, but both are embedded in the skin. C fibers typically innervate
the epidermis while the Aδ fibers innervate
1.2.1 Neuron Morphology and the layer between the epidermis and dermis.
Figure 1.1 shows the morphological and depth
Neural Innervation
differences of the Aδ fiber and the C fiber dendrites. As you can see, the C fibers have fewer
Thermoreceptive neurons are not unlike that dendrites per neuron, and thus a smaller recepother nuerons of the somatosensory system. For tive field than the Aδ fibers.
the most part, thermoreceptors are free dendrite
endings in skin, and thus are primary sensory
Cell bodies of the afferent fibers of cutaneous
organs. They have no specialized epithelial cells thermoreceptors reside in the dorsal root ganor supporting cells [6]. However, recent research glion (DRG) or the trigeminal ganglion on the
has identified a very high concentration of ther- dorsal horn of the spinal cord. The trigeminal
mosensitive TRP ion channels in keratinocytes neuron is particularily sensitive to cold due to
8
CHAPTER 1. CUTANEOUS THERMORECEPTION
Figure 1.2: Both warm and cool stimuli transduce information along the same nerual pathway.
After peripheral stimulation, the afferent fibers
proceed to the DRG where the sensory neurons’
cell bodies reside. Then axons proceed to the Lamina I dorsal horn where they synapse with other
neurons. These neurons project towards different
areas of the ventromedial nucleus of the thalamus:
the posterior portion (VMpo) or the basal portion
(VMb). Both of these pathways then project to
the insular cortex. Adapted from source 14
its high expression of cold-activated TRP ion
channels. Some body surfaces, such as the eyes
and tongue, are innervated with the trigeminal
nerves; those surfaces have increased sensitivity
to cold and to cooling compounds that activate
the cold-activated TRPs [1, 7].
The neural pathways eventually lead to two
different locations of the brain. The pathway
that is specialized for discriminative temperature sensation sends action potentials to the
Figure 1.3: Axons from the Lamina I dorsal
horn synapse to currently unknown locations in
the brainstem, then proceed to the POA on the
anterior hypothalamus. The hypothalamus then
elicits action potentials to induce the proper thermoregulatory responses. Adapted from source 14
insular cortex for processing [10,17]. The pathway specialized for homeostatic control sends
action potentials to the pre-optic area (POA)
on the hypothalamus. Figure 1.2 shows the
pathway of transduction from the peripheral
stimulus to the insular cortex. The afferent
pathways leading to homeostatic control are
the same for rats and humans, but not for all
vertebrates[7, 28].
Niether pathway shown in Figure 1.2 is involved in thermoregulatory responses for overall
TB . Instead these pathways are involved in discriminitive temperature sensation. They allow
us to sense temperature at a specific location
1.2. MECHANISMS OF THERMORECEPTION
9
of our skin, and thus are important for our in- and multiple sclerosis, tend to experience PHS
tearctions with objects in our environment [17]. much more often than healthy individuals. So
For instance, we can discriminate between a what causes PHS?
steaming hot cup of coffee and a comfortably
warm cup of coffee. Then we can make the
decision of whether or not we want to drink the
coffee now, or wait for it to cool first.
Figure 1.3 shows the neural pathway for thermosensory information that elicits homeostatic
responses to maintain proper TB . This neural
pathway is similar to the afferent pathway for
discriminative temperature sense from the peFigure 1.4: C fibers transduce the false heat
riphery to the spinal cord. From the Lamina
that is sensed with PHS. If not enough of the Aδ
I syapse, the action potentials are directed to
fibers are activated, they do not provide enough of
the POA on the anterior hypothalamus. The
an inhibitory impulse to prevent the C fiber from
transducing the false sensation of heat. Adapted
POA also receives sensory information from the
from source 17
deep thermoreceptors. The information from
peripheral and deep thermoreceptors is integrated and interpreted. Then the information
This question can be answered by determinis sent to the posterior hypothalamus which ing a few things. Do thermosensors follow the
sends efferent signals that elicit thermoregula- labeled-line theory of transduction and interpretory responses[14, 17].
tation, or do they follow a pattern-code theory
of transduction and interpretation? When anNeural pathways and neuron morphologies swering these questions, we find that whether a
play key roles our perception of temperature. temperature is preceived as being hot or cold is
Thus, they also play key roles in trandsucing the due to the labeled line theory: the perception of
wrong response to the central nervous system heat is always transduced via C fibers, and the
(CNS)
perception of cold is always transduced via Aδ
fibers. However, we also find that our ability
to distinguish different degrees of hot and cold
Thermal Noise
is due to pattern-code theory of transduction
and interpretation.
Many people have experienced paradoxical
heat sensation (PHS): the skin is exposed to
PHS in healthy individuals occurs in the pecold, but the individual perceives heat instead. riphery. The cold stimulus is sensed by the
Interestingly, persons with certain neurological Aδ fibers, but some C fibers are also activated.
disorders, particularily uraemic polynueropathy The transduction along the C fibers is what
10
CHAPTER 1. CUTANEOUS THERMORECEPTION
induces PHS, not transduction along the Aδ wihtout any of the conditions described above
fibers. Thus PHS is not a problem of central [17].
modulation, but instead occurs when ’noise’ activates a heat-sense neuron [17] This may be
due to the fact that some cold-sensitive TRP 1.2.2 Transient Receptor Proion channels are co-expressed with the warmtein (TRP) Ion Channels
sensitive ion channels in some C-fibers [11].
Interestingly, if a smaller probe or object is
used, a smaller surface area of skin is stimulated and PHS perception is increased. Also,
a greater temperature change induced by the
probe increases PHS perception. Lastly, if preheating of the skin prior to the probe stimulus
increases PHS. The response of increased PHS
to a smaller probe is inverse to what is expected
since the likelihood of activating a C fiber becomes much lower with a smaller probe. This
indicates that the cold Aδ fibers require a summation effect to induce sufficient numbers of
action potentials to actually sense cold. This
also shows that both cold and hot receptors can
be activated by temperature change, regardless
of whether the temperature change is positice
or negative. Cold activation results in inhibition of transduction along the C fibers as shown
in Figure 1.4 [17].
TRP ion channels are transmembrane proteins
that make thermosense possible. However, they
are not solely specific to thermoreception; TRP
channels are also important for chemosense and
for mechanosense. Later on, we will see that
some of the thermoTRPs are also activated by
chemical and mechanical stimuli.
TRP ion channels are constructed in a similar manner to voltage-gated K+ channels. They
are composed of four subunits, and have 6 transmembrane domains referred to as TM1 – TM6.
The C- and the N- terminal tails are cystolic,
and are vital functional components of the ion
channel. The transmembrane domains TM1 –
TM4 are the modulators of activation and control ion gating. TM5 and TM6 form the pore in
the membrane through which ions can flow [18,
19]. TRP ion channels typically allow an influx of many ions which tends to be dominated
Only about 10% of healthy individuals expe- by Ca2+ . The increase in ion concentration
rience PHS under normal conditions. However depolarizes the membrane, and causes action
when all three of the above conditions are met, potentials to fire [19].
the perception of PHS in healthy individuals
increases to 66%. In persons with neuropathies,
There are many subfamilies within the TRP
PHS could be a perihperal or a central phe- family of ion channels: TRPC (canonical or clasnomenom. Some neuropathies have higher in- sical), TRPV (vanilloid), TRPP (polycystin),
ceidences of PHS than others. For instance, TRPML (mucolipin), TRPA (ankyrin-like),
persons diagnosed with, or suspected for mul- TRPM (melastatin), and TRPN (no mechanoretiple sclerosis have a 66% incidence of PHS ceptor potential) [20].
11
1.2. MECHANISMS OF THERMORECEPTION
Subfamily
TRPV
TRP Channel Animals
Temperature Sensitivity
TRPV1
humans, mice, rats, dogs, guinea
Painful heat (> 43◦ C)
TRPV2
TRPV3
TRPV4
TRPA
TRPA1
TRPM
TRPA1*
TRPM8
pigs, rabbits, chickens, WC
frogs, zebrafish, pufferfish, birds,
crocodiles
humans, mice, rats, cows, chickens, WC frogs
humans, mice, rats, chickens, WC
frogs
humans, mice, rats, chickens, zebrafish, pufferfish, WC frogs
humans, mice, rats, chickens, WC
frogs, pufferfish, zebrafish
sea squirts, fruit flies, mosquitos
humans, mice, rats, chickens, WC
frogs, crocodiles
Extreme heat (> 53◦ C)
Ambient heat (> 33◦ C)
Ambient heat (25 − 34◦ C)
Painful cold (< 17◦ C)
(> 27◦ C)
Ambient cold (8 − 28◦ C)
Table 1.1: ThermoTRP channels and thier activation temperatures. As you can see, the TRPA1
channel activates at different temperatures for the sea squirt, fruit fly, and mosquito, than it does for
humans and some other animals. For a sea suirt which resides at the ocean floor, the TRPA1 channel
acts as a warm receptor. Adapted from sources 21,28
The subfamily of TRPC was first identified
in Drosophila, and is activated by phospholipase C signaling. Six temperature activated
TRP ion channels have been identified. TRPV1,
TRPV2, TRPV3, and TRPV4 are all activated
by heating. TRPM8 and TRPA1 are activated
by cooling [11]. All six, when expressed in naive
cells, have the ability to make that cell temperature sensitive. The thermoTRP ion channels,
along with their thermal sensitivites and organisms that express them are listed in Table
1.1.
a 10◦ C increase. The equation to calculate
Q10 , using temperature (T) and rate of ion flow
(Rate):
Q10 =
Rate(T +10)
Rate(T )
Typical voltage gated ion channels have a
Q10 value between two and four: which can be
interpreted as two to four times greater rate of
ion flow through the ion channels when temperature increases by to◦ C. Heat-activated TRP
The flow of ions through a TRP ion chan- channels have Q10 values between 6 and 30,
nel can be quantified, and analyzed using the which is well above a typical ion channel. Inter10-degree temperature coefficient (Q10 ). Q10 estingly, the Q10 values for cold-activated TRP
shows the magnitude of increased ion flow for channels are less than 1. This means, that as
12
CHAPTER 1. CUTANEOUS THERMORECEPTION
Figure 1.5: This figure shows the morphology of the TRP channel. All mammalian TRPs are
structurally very similar even though they have such great diversity in amino acid sequence. The
N- and C- terminal tails are cytosolic, and have distinctive variation. Although the tails are shown
for all the identified TRP channels, only TRPM and TRPV are discussed in this chapter as those
channels are specific to thermoreception. Adapted from source 22
temperature increases, the rate of ion flow ac- 1.2.3
tually decreases. This is paradoxical to most if
not all other ion channels [18].
Warm-Response Ion Channels
TRPV1
Much of the research on thermoTRP ion
channels has focused on TRPV1 and TRPM8.
Thus the sections for TRPV1 and TRPM8 are
much more detailed than the sections for the
other thermoTRPs.
The first mammalian TRP channel discovered was the TRPV1 which is a warm-sensitive
ion channel. Recent studies have identified
TRPV1 in crocodiles and two lizards. In fact,
genetic sequences for TRPV1 in mammals, reptiles and birds are very similar, and all may
1.2. MECHANISMS OF THERMORECEPTION
Figure 1.6: Image of the transmembrane domains and terminal tails for the TRPV1 ion channel. Adapted from source 23
share some some common ancestry with the
Xenopus [27]. TRPV1 is polymodal and also
acts as a nociceptor, and has a heat threshold
of about 43◦ C. Not surprisingly, this is also
the temperature at which most peoples perception of temperature transitions from warm, to
painfully hot. The TRPV1 ion channel has a
Q10 for channel opening of approximately 14.8
during heating, and a Q10 of 1.35 for channel
closing. Thus as temperature increases, the
ion channels open much more often than they
close. This leads to a rapid increase in action
potential firing [18].
TRPV1 is important in the detection of
painful stimuli induced by noxious temperatures and by low pH [21]. Interestingly the
avian TRPV1 produces a receptor that is sensitive to heat- and pH- stimuli, but is not responsive to capsiacin.
13
but non-responsive to pH. Although the ion
channel for TRPV1 is sensitive to capsaicin,
the naked mole rat does not exibit behovior
to show that the animal responds to capsaicin
exposure. Also, chemical exposure does not result in heat hyperalgesia like it does in all other
mammals studied to this point. Heat stimuli
activate C-fibers in the mole rats, and result
in behaviors indicative of pain. However, exclusive excitation of capsaicin-sensitive C-fibers
with heat-stimuli do not result in pain behaviors. The capsiacin activated C-fibers lack a
strong enough response to activate the neural
networks that result in pain-related behaviours.
The naked mole-rat is not the only animal
that has capsiacin sensitive fibers that do not
respond to heat. However, in all other rodent
species studied, all noxious heat-sensitive neurons are sensitive to capsaicin, whereas only
half of the mole rat neurons were activated by
capsaicin [30].
How did the TRPV1 sensitivity diverge from
its common activating stimuli? Naked mole rats
reside in subteranean/enclosed and cramped environments. It is possible due to these cramped
environments, and increased concentration of
CO2 is inspired. In the bloodstream, increased
CO2 leads to increased formation of protons
(H+ ), and acidosis of the blood. This can elicit
a painful response in may tissues. Thus, over
time and constant exposure to environments
that yeild acidic blood, there could be selective pressure for animals to loose nociceptive
response to acid.
The naked mole role expresses a TRPV1 reTRPV1 is susceptible to sensitization followceptor that is sensitive to heat and capsaicin, ing injury or inflammation. Three primary
14
CHAPTER 1. CUTANEOUS THERMORECEPTION
Figure 1.7: TRPV1 sensitization occurs via two molecular signalling pathways. Through the
PKC pathway, NGF increases the sensetivity of existing TRPV1 receptor proteins. Through
the PKCδ pathway, it increases the production and membrane incorporation of TRPV1 receptor
proteins. Adapted from source 15
inflammatory mediators are responsible for
the sensitization: bradykinin, ATP, and nerve
growth factor (NGF). TRPV1 is the primary
site of action for sensitization. Heat hyperalgesia, perceivinga temperature as being hotter than it actually is, is largely absent from
knockout animals that are missing the genetic
inforamtion for TRPV1 [15].
described below. Sensitization occurs primarily
by way of NGF, which binds to the TrkA receptor. This activates a kinase signaling pathway
which first activates PI3 kinase. PI3 in turn
activates protein kinase C PKCδ which then
activates Src. Src kinase binds to and phosphorylates Y200 tyrosine residues on TRPV1. The
SH3 domain of Src binds to sites on both the
C-terminus and the N-terminus. However, only
Figure 1.7 provides a detailed view of the binding at the N-terminus elicits sensitization.
sensitization mechanism for TRPV1 which is In fact, the C-terminus acts as an inhibitor of
1.2. MECHANISMS OF THERMORECEPTION
sensitization by competing for intracellular active Src. The phosphorylation of tyrosine-200
is particularily important in sensitization of the
TRPV1 receptor. It causes intracellular pools
of TRPV1 to integrate with the cell membrane,
thus increasing TRPV1 prevalence [15].
TrkA also activates PLCγ , which then activates PKC . PKC phosphorylates S502 and
S800 sites and results in some sensitization.
Bradykinin (BK) also sensitizes TRPV1 via
this pathways. However, this pathway is minor
compared to the previously mentioned sensitization pathway.
15
TRPV1 channels and induce a noxious stimulus. Capsaicin binds to a region on TM3 for
activation of TRPV1. Capsaicin and other
non-thermal stimulators of thermoTRPs are
discussed towards the end of the chapter [29].
TRPV2
TRPV2 is genetically similar to TRPV1, and
is selective for Ca2+ influx [19]. TRPV2 is
activated by extreme heats (> 53◦ C). Mechanical stretch and insulin growth factor sensitize
TRPV2 by increasing translocation from intracellular pools to the plasma membrane [22].
A region on the C-terminal tail, amino acids This is similar to the primary mechanism of
777–820, binds to PIP2 . When PIP2 is bound to TRPV1 sensitization.
the C-terminus, tyrosine-200 phosphorylation
on the N-terminus is inhibited. The multiple
inhibitory effects of the C-terminus regulate sen- TRPV3
sitization. Mutations at either the Src binding
site, or at the PIP2 binding site, would increase
TRPV3 has an activation threshold of 33◦ C.
sensitization by NGF, and would be more susceptible to suffer from heat hyperalgesia [15]. TRPV3 is also activated by camphor, a biologiAlso, stimuli that increase PLC activity can cal compound that is produced by some plants.
Interestingly, TRPV3 is highly expressed in kersensitize TRPV1 by hydrolyzing PIP2 [21].
atinocytes, and may be involved in secondary
Also, PI3 kinase inhibitors and PKC in- thermosensory cells in many animals. In prihibitors can almost abolish TRPV1 sensitiza- mates, TRPV3 expression is present in both
tion. However, the PKC inhibitor bisindolyl- keratinocytes and in sensory neurons. [11].
maleimide (BIM) more effectively inhibits phosphorylation than other broad spectrum PKC
TRPV3 has been observed to be co-expressed
inhibitors. BIM more specificly inhibits PKCδ , with TRPV1, and may have overlapping funcan integral molecule in the major signalling tions. Some recent studies have shown that anpathway for TRPV1 [15].
imals with knockout TRPV3, have had deficits
in their responses to noxious heat, even though
Natural products such as capsaicin have TRPV1 expression was normal. It is possible
evolved to target the activation regions of the that that the keratinocytes release a molecule at
16
CHAPTER 1. CUTANEOUS THERMORECEPTION
noxious temperatures to assist in activating no- 1.2.4
ciceptive fibers [11]. Also TRPV3 is sensitized
with repeated activation [19].
TRPV4
Cool-Response Ion Channels
TRPA1
TRPA1 is activated at extremely cold temperatures (< 17◦ C). Interestingly, TRPA1 is
expressed in both Aδ fibers and in C fibers.
TRPA1 is also shown to be co-expressed with
TRPV1. Both are bimodal thermo/nociceptors
[11].
TRPV4 is activated between 25◦ C and 34◦ C.
TRPV4 however becomes desensitized with prolonged or repeated exposure, which is different
than TRPV1 and TRPV3 [11]. TRPV4 also
looses heat sensitivity if it is excised from a cell.
This indicates that TRPV4 probably requires
an intracellular signaling molecule to make it TRPM8
temp-sensitive [18]. Mutations between TM2
and TM3 of TRPV4 result in inhibited or no
TRPM8 was first identified in the prostate. It
activation [29].
is a non-selective ion channel. However, Ca2+
tends to be the dominant ion that flows in
The N-terminus is responsible for descrimi- due to a stronger gradient [19]. TRPM8 is
nating between activation via heating vs. acti- also upregulated in prostate cancer cells, and
vation via phorbol esters. This indicates that could possibly be used as a diagnostic marker
TRPV4 has multiple mechanisms of activation for identifying prostate cancer [20]. To this
[19]. TRPV4 is activated also by hypoosmolar date, homologs of the mammalian TRPM8 ion
challenge, and metabolites of arachidonic acid channel have been identified in birds, crocodiles
or anandamide. When activated by arachido- and frogs, but not in lizards [27].
nate, there is a time delay between stimulus and
The TRPM8 ion channel is activated at a
activation. This is due to the fact that arachiwide range of cold temperatures: 8◦ - 28◦ C.
donate must first be converted to its active
When activated, TRPM8 allows an influx of
metabolite, arachadonic acid. This conversion
Ca2+ , as well as other ions. As temperature
takes place via Cytochrome P-450 [29].
increases, TRPM8 has a much higher Q10 for
channel closing, 9.4, than it does for channel
Taxol can induce painful peripheral neu- opening, 1.2 [18]. So if the temperature inropathies in rats, that is succesfully treated creases, almost 10 ion influx channels close for
with gene splicing of the TRPV4 gene. Thus every 1 ion influx channel that opens. So at
TRPV4 may also be polymodal, and could be high temperatures very few, if any, action poa signifcant ion channel in nociception [21].
tentials are generated.
1.2. MECHANISMS OF THERMORECEPTION
Phoshpatidylinositol
4,5,–bisphosphate
(PIP2 ) is the intracellular molecule that interacts with the C-terminus to facilitate channel
opening. PIP2 within the cell can activate the
chanel without an external stimulus. Cooling
seems to increase the TRPM8 channel’s affinity
for PIP2 at C-terminus. Once activated,
Ca2+ flows in through TRPM8 and activates
phospholipase C (PLC) which hydrolyzes
PIP2 . Hydrolysis results in a decrease in active
PIP2 which leads to inhibition of the TRPM8
channel. Thus the activation of TRPM8 is brief.
TRPM8 is inhibited by 2-aminoethoxydiphenyl
borate (2–APB). 2–APB inhibits many Ca2+
influx channels [20].
17
Mn2+ , Co2+ , and Zn2+ , to replace Ca2+ as a
coagonist for icilin. However, none elicited any
responses from TRPM8. Also, extracellular
Ca2+ shows no ability to activate TRPM8 by
itself. Thus it is likely that as Ca2+ flows into
the cell, it has some action intracellularly to
act as a cofactor for ilicin. Icilin readily potentiates cold-evoked currents for an increase
in cytoplasmic Ca2+ concentration, which then
activates a positive feed-back loop. The result
is a rapid increase in Ca2+ concentration [29].
The delayed activation of TRPM8 via icilin
provides cells expressing TRPM8 with the ability to generate distinct waves of Ca2+ concentration. These waves would be generated if
an endogenous icilin or iciln-like molecule were
present, then some other molecule or stimulus
invoked slight Ca2+ influx, then priming the
cell for icilin activation. Inflammatory agents
can activate PLC pathways, which would induce such a response. This allows icilin to be
an agonist that activates after some coincident
stimulus allows Ca2+ influx [29].
TRPM8 is also sensitive to some chemical
compounds: menthol and eucalyptol, and is
super-sensitive to icilin which is chemcially nonrelated to the other two chemical agonists. In
fact icilin is about 200 times as potent. Menthol or cold directly activates TRPM8 in the
absence of extracellular Ca2+ , but TRPM8 is
essentially non-responsive to icilin in the absence of extracellular Ca2+ . Since TRPM8 is
modulated by phospholipase C (PLC), it has
the ability to be polymodal. This is a common
The amino acids at N799, D802, and G805 in
theme amongst TRP ion channels. The intra- the cytoplasmic loop between TM2 and TM3
cellular loop that connects TM2 and TM3 is domains of rat TRPM8 are necessary for icilin
essential for icilin activation [29].
activation. Interestingly, intracellular molecules
necessary for TRPV1 bind to analagos sites beTRPM8 gating via icilin is delayed in a man- tween the TM2 and TM3 domains. Also, mutaner similar to that seen in TRPV4 activation tions in this region on TRPV4 inhibit TRPV4
by arachadonic acid metabolites. Icilin activa- activation. Thus, even though there is little
tion is dependent on either some Ca2 + influx conservation between the thermoTRP channels
through open TRPM8 channels, or via release in their amino acid sequences, structural and
of Ca2 + stores into the cytosol Many divalent functional topology involved chemical binding
cations have been tested, Mg2+ , Sr2+ , Ba2+ , and ion gating are highly conserved [29].
18
CHAPTER 1. CUTANEOUS THERMORECEPTION
Menthol and eucalyptol are also agonists of
TRPM8. Menthol activates TRPM8 in a similar manner as cold temperatures, it shifts the
voltage dependent activation curve toward physiologic membrane potentials [20].
The combination of cold-sensitive and hotsensitive neurons provide a wide range of temperature senstivity. Figure 1.8 shows how these
channels have somewhat overlapping temperature sensitivties, and thus provide a continyous
range of temperature sensation.
is that they encode information via the pattern
code theory of transduction and interpretation.
Thermoreceptors behave in a very distinct way
to both changing and static temperatures. As
temperature changes, the neurons fire action
potentials in groups, that form very distinct patterns which correspond to certain temperatures;
these are referred to as bursts [8,9]. Bursts consist of a number of quickly generated action
potentials followed by a period of silence, which
is referred to as the interburst period. The
sizes and frequencies of these bursts are dependent on the temperature, and the neuron [8,
26]. To fully understand bursting, we must first
understand some key concepts:
• Fast activating system; and
• Slowly oscillating internal system.
The fast activating system is what generates
the typical action potential. It occurs when a
stimulus elicits a change in membrane potential,
and firing occurs [8].
The slow oscillating system is likely due to
fluctuations in intracellular Ca2+ . The fluctuited ranges of activation. However, together they
ations in ion concentration continually change
provide thermal information for a very wide range
the membrane potential within the nueron. The
of temperatures. Adapted from source 23
change in intracellular ion concentration results
in a wave pattern of membrane potential. At
the peak of the wave pattern, the ion concen1.2.5 Bursting
tration is high, and thus the membrane can
be easily depolarized [8]. The dashed lines in
One of the main reasons thermosensitive neu- Figure 1.9 show the internal oscillation of a
rons have such wide temperature sensitivites, thermosensory cell. The solid line shows how
Figure 1.8: Individual TRP receptors have lim-
19
1.2. MECHANISMS OF THERMORECEPTION
spikes are a result of noise, combined with the
slow internal oscillation [8]. Figure 1.10 shows
a cold-sensitive neuron responding to different
static temperatures.
For cold-sensitive neurons: The lower the
temperature, the more normal the burst pattern
appears. The frequency of impulses is lower,
but more impulses are grouped into each burst
[2,9].
Figure 1.9: The dashed line shows the oscillating
ion concentration. At the peak of the oscillation,
the membrane can be depolarized by a number of
minor stimuli, or possible even by the oscillation
itself. Adapted from source 8
For heat-sensitive neurons: The higher the
temperature, the more irregular the burst pattern. There is a higher frequency of impulses,
but with fewer impulses per burst [2,9].
The bursting patterns allow for us to perceive a wide range of temperatures. However,
mild stimulus can invoke a false positive, and animals also have the ability to adapt to temperatures.
result in action potentials firing.
The patterns formed from bursts varies for
each neuron at each temperature. Thus, the
ability sense a wide range of temperatures is
dependent on multiple neurons sensing temperature within their ranges. When a burst of
action potentials reaches the end of a neuron, it
results in more neurotransmitter being released
than when a single action potential reaches the
end [8].
For temperatures above the sensory midpoint,
the spike pattern becomes aperiodic, and continues to become more irregular as temperature
increases. Some double spikes also begin to
show up and other spikes are skipped as temperature increases. At high temperatures, all
1.2.6
Perception
tion
and
Adapta-
Adaptation to temperature changes occur at the
sensory neuron. Humans can achieve complete
adaptation if:
• The temperature limits are between 30 36◦ C, on a 15cm patch of skin, or;
• The temperature limits are between 33 35◦ C, on the whole body.
20
CHAPTER 1. CUTANEOUS THERMORECEPTION
Perception of heat also adapts. When the
temperature change is not perceptible, then
the rate of adaptation of the sensory neuron
is equal to the rat of adaptation to perception. Psychophysical studies on humans have
developed the following relationship between
temperature change and perception, called the
psychophysical power law. Estimated temperature sensation (P) is related to the magnitude
of thermal stimulus (∆T ) [6].
P → k∆T n
When radiant heat is applied to an individual’s skin, warmth perception can be assessed
estimating the magnitude of the temperature
[6]:
• A stimulus applied for 2 to 6 seconds resulted in an average exponent n = 0.87 [6].
• The same temperature stimulus applied for
12 seconds resulted in an average exponent
n = 1.04 [6].
• These findings suggest that sensory adaptation occurs during the heat stimulation,
and that perception may have a slight lag
time. When the exponent is less than one,
the perception of heat is slightly less than
it’s magnitude. However, over a longer
time, the perception of heat is closer to
the actual heat, or slightly above.
Cold receptors show little, or no, dynamic
activity if the rate of cooling is less than
0.02◦ C/sec. This is because the rate of temperature change is equal to the rate of sensory
adaptation, and thus there is no perception of
temperature change. However, higher cooling
rates are typically perceived [5]. Receptors that
function like this are termed dynamic thermoreceptors which have a very distinctive response
during temperature change, but adapt quickly
under static conditions [14].
1.2. MECHANISMS OF THERMORECEPTION
Figure 1.10: The chart on the left shows the
shape of action potentials at that temperature.
At high temperatures, the action potential takes
more time to initiate, and shows a broader peak.
The low temperature action potentials are initiated immediately, and produce very sharp spikes.
The chart on the right shows the bursting patterns
at the static temperatures associated with the action potentials on the left. The bursting patterns
change as the temperature changes. Each nueron
was allowed to stay at the static temperature for
2 minutes prior to initiating a measurement. This
prevents the accidental detection of the neuron’s
response to temperature change. Adapted from
source 8
21
22
CHAPTER 1. CUTANEOUS THERMORECEPTION
Unique Thermoreception: Sharks have a very unique system for detecting temperature.
An organ called the ampullae of Lorenzini is electrosensitive, and is also equiped to detect temperature
changes. The surface skin of sharks has gel filled canals that proceed to the ampullae which is innervated
by the CNS. The gel within these canals has thermoelectric properties similar to those of a semiconductor.
Thus the gel acts as a medium for which thermal information is trasnferred from the environment to the
ampullae [13, 25].
23
1.3. SUMMARY
1.3
Summary
their respective TRP ion channels. Identifying
chemical activators of the other thermoTRPs
could be very important for future research
Thermoreception is a vital sensory tool that can to reveal more information about their mechabe used for both thermoregulation and discri- nisms of action.
minitive temperature sense. The thermoTRP
channels are fundemental to the production of
Also, future research is likely to focus on the
action potentials that allow us and other ani- interaction of heat with the TRP ion channels.
mals to perceive temperatures.
Currently, the actual mechanisms of activation
are a conglomeration of theories, that have yet
ThermoTRPs in many species have to be regularily reproduced. Promising theories
analagous structures despite variations in for future research involve two primary paths: 1.
amino acid sequence, and also respond to Thermal properties of the TRP proteins underthe same or similar temperature ranges. The goe morphological changes at thier activation
ranges of individual TRP channels are limited, temperatures, and/or; 2. Shifting of membrane
but the combination of all the thermoTRPs potential due to changes in temperature.
allow for sensation across a very broad range.
Also, more research will likely be done on
TRP channels overall allow for non- the possibility of thermpTRPs being expressed
descriminitive influx of ion, however, Ca2 + in non-neural cells. It has already been demontends to have the largest flow into the cell. strated that TRPV3 and TRPV4 are present
Within each cell, different mechanisms result in in keratinocytes of mammals. But are other
action potentials firing for each different ther- thermoTRPs present in other cells that could
moTRP.
act as secondary sense organs?
The rate, and bursting patterns of action potentials are interpreted by the CNS to detect
different temperatures. Typically, bursting pat- 1.4
terns for cold responsive neurons become more
ordered as temperature decreases, the opposite
1.4.1
is true for warm-sense neurons.
A number of no-thermal stimuli can activate the thermoTRPs making those ion channels polymodal. Capsaicin is an activator the
TRPV1 and menthol is an activator of TRPV8.
These chemical compounds have been very useful in identifying activation mechanisms for
Review
Multiple Choice
1. In what animal was the first TRP ion channel discovered?
(a) Humans
(b) Paramecium
(c) Rats
24
CHAPTER 1. CUTANEOUS THERMORECEPTION
(d) Drosophila
2. Which of the following qualities describes
a cold-sense neuron?
(a) myelinated Aδ fibers; 1.5 - 3 µm diameter axon; innervate skin at the
interface of the dermis and epidermis
(b) unmyelinated Aδ fibers; 1 - 2 µm diameter axon; innervate skin between
the keratinocytes of the epidermis
(c) unmyelinated C fibers; 1 - 2 µm diameter axon; innervate skin between
the keratinocytes of the epidermis
(a) between TM2 and TM3
(b) C-terminus
(c) N-terminus
(d) none, there is very little conservation
amongst the thermoTRP ion channels
6. Which agonist of TRPM8 elicits the largest
response?
(a) menthol
(b) menthone
(c) capsaicin
(d) icilin
(d) myelinated C fibers; 1.5 - 3 µm diameter axon; innervate skin at the
interface of the dermis and epidermis 1.4.2
3. Which type of temperature response is
transduced through the Lamina I in the
spinal cord?
(a) discriminitive temperature sense
(b) thermoregulatory temperature sense
(c) both a and b
(d) neither a or b
4. Which of the following is a strong inhibitor
of TRPV1 sensitization?
(a) protons
(b) PKCδ
(c) BIM
(d) capsaicin
5. Many TRP channels show structural conservation of with region?
Comprehensive
1. A student has isolated two seperate thermosensitive neurons of the same length.
He is sure that one neuron is cool-sensitive,
and one is warm sensitive. The only equipment available to the student is an electrode and a hot plate. The electrode can
accurately measure when an action potential is received as well as the time interval between action potentials. How might
this student identify which neuron is coolsensitive, and which is warm-sensitive?
2. Briefly describe how thermosense is a combination of both the labeled line theory
and the pattern-code theory of transduction and integration.
3. Describe how the major sensitization pathway for TRPV1 occurs. How does it differ
from the minor senesitization pathways?
1.4. REVIEW
4. Cells expressing TRPM8 sometimes show
a wave-like pattern of Ca2+ concentration.
How is this wave pattern generated, and
how does this effect the cell’s ability to
respond to cold stimuli?
5. Action potentials transmitted along a hot
sensitive neuron are measured. The pattern of action potentials at 30◦ C are showing some grouping. However, there is little
space between groups, and few action potentials per group. What would you expect
to see if the temperature was increased to
40◦ C?
25
26
CHAPTER 1. CUTANEOUS THERMORECEPTION
Bibliography
[1] McKemy, David D. and Neuhausser, Werner [6] Hensel, Herbert. Thermoreceptors. Annual
M. and Julius, David, Identification of a
Reviews Vol. 36, 1974, pp233–249.
cold receptor reveals a general role for TRP
channels in thermosensations. Nature Vol. [7] Nakamura, Kazuhiro and Morrison, Shaun
416, March 7, 2002, pp. 52–58.
F. Central efferent pathways mediating skin
cooling evoked sympathetic thermogenesis in
[2] Adair, Robert K., A model of detection
brown adipose tissue. American Journal of
of warmth and cold by cutaneous senPhysiology Vol. 292, 2007, pp. 127–136.
sors through effects on voltage-gated membrane channels. Proceedings of the National [8] Roper, Peter and Bressloff, Paul C. and
Academy of Sciences Vol. 96, October 12,
Longtin, Andre. A Phase Model of Temper1999, pp. 11825–11829.
ature Dependent Mammalian Cold Recep[3] Reid, Gordon and Flonta, Maria-Luiza.
Cold Current in thermoreceptive neurons.
Nature Vol. 413, October 4, 2001 pp. 480.
tors. Neural Computation Vol. 12, 2000, pp.
1067–1093.
[9] Iggo, A. Cutaneous Thermoreceptors in Primates and Sub-Primates. Journal of Physi[4] Cooper, K. E. Molecular Biology of Therology Vol. 200, 1969, pp 403–430.
moregulation: Some historical perspectives
on thermoregulation. Journal of Applied
Physiology Vol. 92 Issue 4, April, 2002, pp. [10] Boulant, Jack A. Physiology and Pathophysiology of Temperature Regulation. Chap1717–1724.
ter 6: Neural Thermal Reception and Regulation of Body Temperature. World Scien[5] Kozyreva, T. V. and Tkachenko, E. Y. and
tific Publishing Co. 1998.
Kozaruk, V. P. and Latysheva, T. V. and
Gilinsky, M. A. Efects of slow and rapid
cooling on catecholamine concentration in [11] Dhaka, Ajay and Viswanath, Veena and
arterial plasma and the skin. American JourPatapoutian, Ardem. TRP Ion Channels
nal of Physiology: Regulatory, Integrative
and Temperature Sensation Annual Review
and Comparative Physiology Vol. 276, 1999,
of Neuroscience, March 15, 2006, pp. 135–
pp. 1668–1672.
161.
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[12] Reid, Gordon and Flonta, Maria-Luiza.
ing with TRP channels. Nature: Chemical
Ion channels activated by cold and menthol
Biology Vol. 1 No. 2, July 2005, pp. 85–92.
in cultured rat dorsal root ganglion neurons.
Physiology: Neuroscience Letters, 2002, pp. [19] Ramsey, Scott I. and Delling, Markus and
Clapham, David E. An Introduction to TRP
171–174.
Channels. Annual Review: Physiology Vol.
68, 2006 pp. 619–647
[13] Seebacher, Frank and Franklin, Craig E.
Physiological mechanisms of thermoregulation in reptiles: a review. Journal of Comparative Physiology and Biology Vol. 175,
July 27, 2005, pp. 533–541.
[14] Romanovsky, Adrej A. Thermoregulation:
some concepts have changed. Functional architecture of the thermoregulatory system.
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology Vol. 292, 2007, pp. R37–R46.
[15] Zhang, Xuming and Huang, Jiehong and
McNaughton, Peter A. NGF rapidly increases membrane expression of TRPV1
heat-gated ion channels The EMBO Journal
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[16] Lumpkin, Ellen A. and Caterina, Michael
J. Mechanisms of sensory transduction in
the skin. Nature Vol. 445, February 22, 2007,
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[17] Susser, Ehud and Sprecher, Elliot and
Yarnitsky, David. Paradoxical heat sensation in healthy subjects: peripherally conducted by Aδ or C fibers?. Brain: A Journal
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[18] Voets, Thomas and Talavera, Karel and
Owsianik, Grzegorz and Nilius, Bernd. Sens-
Chapter 2
Distance Thermoreception
2.1
Introduction
Distance thermoreception is the detection of
electromagnetic waves ranging in length between 1mm to 0.7µm. Wavelengths within this
range are longer than can be detected by human visual perception, but are absorbed by our
skin, leading to the sensation of warmth. Yet,
as biology continues to demonstrate, other animals have adapted specialized anatomy which
exploits this particular spectrum of energy to
give them a prespective of their environment
which is inaccessible to those with sight only in
the "visible range."
An initial investigation into the discovery
and properties of infrared will set the stage for
the chapter as we look into the different structures and neuronal processing animals have
developed to detect the energy output from the
infrared spectrum.
2.2
a young boy, followed in his father’s footsteps
as a musician. Despite his success as a musician and composer, William had an interest in
astronomy which led to the discovery of the
planet Uranus through a telescope of his own
design and creation. During an experiment using different lenses for his telescopes, he felt
a greater heat when little light was shining
through the prisms and little heat when light
was shining through. Being quite inquisitive,
he set up a experiment where he measured the
different temperatures from the different colors
of light split by a prism. He noticed that the
temperature difference between the ambient air
and when the thermometer was placed in the
different colors of light was the greatest in the
area just outside of the red in an area of light
"unfit for vision".[9] It was in this experiment,
published in the Philosophical Transactions of
the Royal Society of London in 1800, when the
world was first made aware of a spectrum of
light past the visible color red: infrared.
Discovery of Infrared
Friederich Wilhelm Herschel was born in Hannover, Germany on 15 November 1738 and as
29
30
2.3
CHAPTER 2. DISTANCE THERMORECEPTION
The Physics
frared
of
In-
Infrared radiation is emitted by any object
which is warmer than about -273◦ C (0 K) and
falls along the continuum of electromagnetic
radiation at wavelengths just longer than those
in the visible spectrum, ranging from approximately 0.7 to 300µm. Wein’s Law helps to
explain the relationship between temperature
and wavelength of radiation and states that
Figure 2.1: The cloud is an infrared image of dust
the maximum wavelength of electromagnetic heated only from distant starlight. Adapted from [11]
radiation emitted by an object is equal to
2.897x103 m K/Temperature (K). Therefore, the
3. Far infrared (10µm-1mm) At this end of
wavelengths emitted in the infrared spectrum
the infrared spectrum, very little penecorrespond with objects which have relatively
trates our atmosphere due to its high abcool temperatures compared with those experisorbance by water. Though it is very efenced in the solar system and beyond.[11]
fective in astronomy where imaging the
cold expanses of space has enhanced our
The infrared spectrum can be divided into
knowledge of the universe and brought us
three different ranges of wavelengths and are
images of space we would not otherwise be
based on the different properties and effects of
able to detect. (Figure 2.1)
the radiation.
1. Near-infrared (0.7-2.5µm) These wavelengths are the closest to the visible spectrum and are not felt as heat. It also includes wavelengths used by the remote controls in your electronic equipment.
2. Mid infrared (2.5-10µm) This is considered
the ’thermal imaging’ range. It is perceived
as heat by people and used by animals and
heat seeking military weapons for ’sight’.
It is also the range in which it is readily
absorbed by water.
Although this wavelength of energy was not
formally discovered until William Hershel was
able to define and measure it in 1800, other
species have known what we have not for millions of years. Animals from vertebrates to
beetles perceive infrared wavelengths and are
able to make critical decisions based on its information. We, on the other hand, have just
begun to tap into the information it can provide.
Police use it to find indoor drug operations [3];
physicians, to detect increased blood supply
that feeds cancerous tumors [1]; scientists, as
31
2.4. BEETLES AND INSECTS
a census method for determining populations
of bats [10]; and engineers, to detect material
variations which could result in failures [18]. Although we are just now discovering these uses
through budding technology, we need to look to
the animals which have optimized its use if we
are to expand our knowledge and application.
From here forward, we will look at how beetles,
insects, and vertebrates use infrared, as well as
the structures and nervous system processing
which makes it possible.
Figure 2.2: The wavelengths of radiation able to
2.4
Beetles and Insects
2.4.1
pass through the atmosphere, 3-5 µm and 8-12 µm,
correspond with the peak sensitivity of the IR sensory
organs in m.acuminata. Adapted from [4]
The
jewel
beetle,
Behavior
Melanophila acuminata
General
Jewel beetles, one of the largest families of beetles, are so named due to their irridescent coloration which has been prized in jewelery making and as a decorating medium. The different
coloration is not attributed to pigmentation of
the exoskeleton, but rather the unique texture
which reflects differing wavelengths of light. Besides their evident beauty, the jewel beetles
are primarily wood borers and can be found
throughout the globe in a variety of different
trees as well as in the framing of your home and
your antique wooden dining room table. With
competition high for finding wood not inhabitated by hundreds of other beetles and insects,
one specics, m. acuminata, has developed an
ability to detect infrared as a means by which
to beat the competition.
Melanophila acuminata are found among the
dying trees after a forest fire. The beetles mate
near the fire and oviposit their young larvae
in the freshly burned back. In the deadened
bark, the larvae are free from competition and
can thrive in the absence of the tree’s natural defenses.[16] The burnt forest also allows
for a unique microclimate. The lack of shade
from the leaves and needles allow more sunlight
to reach the blackened wood and undergrowth
which absorbs the heat from the sun more effecitvely and results in higher ambient temperatures. [14] It is here where the young larvae
thrive,free from predators and competition, on
the fungi and bacteria which begin to grow
in the warm and nutrient rich environment.[8]
Since the likelyhood of having its own resident
forest burn is remote, m. acuminata have devel-
32
CHAPTER 2. DISTANCE THERMORECEPTION
corresponds to a wavelength of 3 µm.[4](Figure
2.2)
Paired pit organs containing 50-100 sensilia
Figure 2.3: The exposed sensory pit of m.acuminata. are located on the underside of the hind legs
Adapted from [19]
in the mesothorax. These pits are covered by
the legs when the beetle is walking along the
oped sensory pits which can detect the radiation ground, yet in flight, the beetle’s legs lift to
emitted from a forest fires over 50 miles away. expose the pit organs.(Figure 2.3) Each of
the sensillium are innevated by a single epidermal sensory neuron housed in a mesocuticular
sphere whcih is suspended by an enducuticular stalk.[8] (Figure 2.4) Associated with the
Mechanism
sensillia are wax glands which keep the sensilla
free from dirt and smoke and may help reduce
The mechanism adapted for detecting IR by m. dessication and cooling of the sensillum duracuminata converges at a wavelength of 3 µm. ing flight. The actual method by which the
The selection for this wavelength is facilitated beetles detect heat is through a paired thermoby two factors: 1) the atmospheric absorbance mechanical transduction method. When IR
of wavelengths and 2) the temperature of for- is absorbed by the mesocuticular sphere, the
est fires. As mentioned in the section on the fluid inside of the sphere is heated causing it
physics of radiation, earth’s atmosphere effec- to expand. The expanding fluid pushes on the
tively blocks much of the electromagnetic radia- walls of the mesocuticular sphere and causes
tion except for those wavelengths in the visible the dendrite to move by as little as 1 µm. The
and infrared spectrum. If we look more closely sensitivity of the dendrite is enhansed by its
at the IR spectrum, wavelengths between 3-5 constriction in the cuticle. This ensures that
µm and 8-12 µm are allowed to pass, unim- any slack in the pore surrounding in the denpeeded while much of the rest is blocked. Addi- drite is removed and any movement due to the
tionally, the temperature of a forest fires ranges expansion of the mesocuticular sphere creates
between 435 and 1150 ◦ C. This temperature a neuronal response.[19]
33
2.4. BEETLES AND INSECTS
Mechanism
To be completed...
• analogous to labial thermosensor organs in
BOID SNAKES, unique in insects
• simple exposed cutaneous thermoreceptor
• ir photons -> heating -> receptor activity
Figure 2.4: A cutaway view of the sensillium. The
diameter of the sphere ranges from 12 to 18 µm and
the stalk is 1.5 to 2 µm in diameter. The dendrite
is composed to two distinct regions: 1-the outer dendritic segment (DOS), and 2-the inner dendritic segment
(DIS). Adapted from [19]
• four abdominal recepters,
• intervated with a thermosensitive multipolar neuron
• primary dendrite branches
• 800 densely packed terminals
Evolution
• significant mitochondria density
• threshold at 40mW/cm2 , 47ms
2.4.2
The ‘Fire Beetle’, Merimna
atrata
Evolution
General
To be completed...
Behavior
To be completed...
To be completed...
2.4.3
The ‘Little Ash Beetle’,
Merimna atrata
General
To be completed...
34
CHAPTER 2. DISTANCE THERMORECEPTION
Behavior
Behavior
To be completed...
To be completed...
Mechanism
Mechanism
To be completed...
To be completed...
• air filled inner chamber, not unline pit
vipers
• complex exposed cutaneous thermoreceptors
Evolution
To be completed...
Evolution
To be completed...
2.4.5
Butterflies
General
2.4.4
Vinchuca ‘The Bloodsucking Bug’, Triatoma infestans Butterflies are heliotherms, regulating their
body temperatures with the sun. This is certainly quite effective as we know from our own
General
experiences when we move into the sun to warm
up or seek shade on a hot day. We also know
To be completed...
what happens when we spend too long in the
sun. Fortunately, we are able to reasonably
• Chagras disease
tolerate a wide range of exposure to the sun’s
• ir sense in combination with olfaction to radiation, but the delicate structures of a butterfly are not so forgiving. The butterflies must
target prey at night
be able to maintain a balance between maintain• thermal sense located in antennae
ing an optimal body temperature and avoiding
• primarily used for short distance orienta- excessive radiation which can cause dessication.
The wings are an ideal structure for providing a
tion
thermosense to the body of the butterfly acting
• warmth -> extension of proboscis
as an early warning dector. Since the body of
2.4. BEETLES AND INSECTS
the butterfly is more massive than the wings,
it takes longer for radiative heating to effect a
temperature change. The wings, which have
little mass, can heat 30 times faster than the
thorax during initial exposure [17]. This makes
the wings perfect detectors of radiation; providing instantaneous information regarding the
current radiative heating capisity of the sun.
This allows the butterfly to take preimptive
measures such that its body does not overheat.
The antennae too are also able to provide information about the environment. However,
because the antennae lack a large surface area
from which to detect radiation, they utilize
other specialized structures to detect the combined effects of heat and humidity. We will look
at how behavior is a function of wing coloration,
how the different structures of the wings affect
heating properties, and the sensitivity of the
structures which allow the butterfly such regulation. Finally, we will look at the structure
of the antaenna to see how it is able to provide
hydro and thermo sense to the butterfly.
35
the wings. When the radiation intensity causes
temperatures above that of the optimal body
temperature of 40◦ C, the butterfly will close
its wings slightly. This response decrease the
angle which the solar radiation strikes the wing
and therefore reduces the effects of heating. If
the radiation reaches temperatures above 46◦ C,
butterflies will either fly away or rapidly flutter
their wings to reduce heating and maximize convective cooling. This behavior is initiated well
before the butterfly could experience an internal
rise in body temperature and will be performed
when only a small section of wing is exposed to
these increases in radiation.[17] The wings will
also close when exposed to lower intensities of
radiation equating to temperatures less than
30◦ C within one second after exposure. This
behavior is reactionary and illustrates that the
butterfly is not always responding to a particular threshold of radiative temperature, but can
detect change. By being able to detect a rate
of warming, ∆T emperature/∆T ime, the butterfly can react before damage can occur.[17]
In addition to responding to solar radiation,
some butterflies, sample the current radiative
conditions and adjust their wings to an angle
Behavior
optimal for appropriate heating. Upon landing,
butterflies will move their wings up and down
A butterfly perched on the tip of a flower gen- until finally settling on a single angle. This
tly adjusting its wings up and down is more angle is then maintained.[17] General basking
than a display of its beauty. These seemingly behaviors correspond with wing coloration.[15]
inconsequential movements allow the butterfly
to sample the radiation which can heat and
1. Dorsal basking is performed by butterflies
eventually destroy its body, as well as use that
whose dark colored wings allow for more
radiation to warm its body to optimal temperabsorption than lightly colored wings. The
atures for metabolic processes and flight. At
wing veins can then take the warmed blood
angles perpendicular to the incident rays of radiback to the rest of the body to keep the
ation, the maximum amount of radiation strikes
butterfly at an optimal body temperature.
36
CHAPTER 2. DISTANCE THERMORECEPTION
2. Conversely, white winged butterflies perform body basking. These butterflies,
whose wings are unable to absorb must
radiation, instead use their wings like reflectors to concentrate the radiation back
unto their bodies.
3. An intermediate between the dorsal and
body basking butterflies is the lateral
baskers. These yellow winged butterflies
can not absorb as must radiation with
their wings as the dark colored butterflies and are not as efficient at reflecting
the sun back unto their bodies. Instead,
these butterflies operate much like a green
house. They close their wings, warming the
trapped air with the radiation absorbed by
their thorax.
Mechanism
The anatomy of butterfly wings is inhereantly
fraglile and leaves little room for bulky thermoreceptors. The butterfly therefore uses two
different structures to regulate and detect the
heat absorbed from solar radiation: 1) the surface anatomy of scales and pigmentation, and 2)
unmylenated multipolar neurons. We will begin
our analysis of these two factors with the outer
surface features. Although not strictly regarded
as a sensory organ, the scales and pigmentation
on the wings in some species selectively absorb
and emit radiation at wavelengths and temperatures which passively maintain optimal body
temperatures. The wings of Prepona meander,
a tropical butterfly, absorb wavelengths in the
visible spectrum, then falls to less than 2 percent at wavelengths above 1µm. However, as
the wavelengths continue to increase in the
infrared spectrum, there is a strong peak of
absorbance at 3µm, 6µm, and a leveling off
around 35 (????) absorbance.[2] These wavelengths correspond to sensitivities we have observed in other animals due to the atmospheric
absorption and emission. However, higher temperatures have shorter wavelengths which could
have adverse effects on the butterflies. In other
words, if the wings absorbed radiation where
there were best suited, at 50◦ C, their bodies
could heat to temperauratures above those that
are viable. The wings fortunately, like all things
above 0◦ K, emit radiation as well. The scales
and pigment of the wings have an exponential
increase in their emmission of radiation corresponding with temperatures above 45◦ C. So,
although the wings may be absorbing radiation
which has the ability to provide leathal amounts
of heat, it is at these temperatures that the butterfly radiates back more thermal energy than
it is receiving and is ablt to maintain its body
temperature at the optimal 40◦ C.[2]
The second anatomical feature of the wings,
and one that is more accurately defined as a
thermoceptor are unmylinated, multipolar neurons. The dendrites run parallel along the veins,
terminating at different locations throughout
the wing. Although these types of cells typically
act as mechanoreceptors, those in the wings of
butterflies are not associated with any other
structure nor do they have any neurosecratory
vessicles. These dendritic endings, altough not
associated with any other structure are classified as Type II receptors and have similiar
2.5. VERTEBRATES
37
morphology to the sensory neurons found in
the thermosensitive pits of vipers.[17]
Evolution
2.5
Vertebrates
2.5.1
Pit Vipers
General
Figure 2.5: The arrows point to the three therBehavior
mosensing pits situated between the nose leaf and pads.
Adapted from [12]
Mechanism
their prey, the bats will circle the animals, making low passes, for up to five minutes. Once
the bat lands, it will stalk the length of their
2.5.2 Boas
prey scanning back and forth for several minutes. The bats tend to get their blood from the
General
flank or neck, but have been observed drinking
from the ear, armpit, udder, vulva, tail, or upBehavior
per part of the leg.[6] Although this behavior
does not necessarily meet with many or our
Mechanism
preconceived ideas regarding the vampire bats
less than appeasing diet, it does correlate well
Evolution
with the abilities of their thermosense. Vampire
bats responds to radiation down to 0.5 x 10− 4
2.5.3 Vampire Bats
W cm− 2 which equates to a distance of 16 cm
for the body temperature of humans.[12] The
General
threshold of detection for radiation correlates
well with the bats behavior: once they land, a
Behavior
closer scan of the body will indicate the location
where the body is the warmest and therefore
Vampire bats typcially prey on large livestock the blood is closest to the surface and more
such as cattle and sheep. Before landing on accessible.
Evolution
38
CHAPTER 2. DISTANCE THERMORECEPTION
which are innervated by a sparse network of
blood vessels. In addition to structural differences, the pits are cooler than the rest of the
head. Situated very close to the eyes, which
are maintained at a temperature of 37 ±0.6
o C, the pits are insulated by the connective
tissue are are maintained at temperatures of
29 ±0.6 o C, a 9 degree difference.[12] The temperature difference maintained by the bats pits
provides contrast with the temperature of its
prey and limits possible interference with its
own radiation emittance. (Figure 2.6)
Figure 2.6: The temperature differences on the bat’s
face–dark center ring: 29o C; Center spot and grey outer
ring: 33o C; Area between ears and eyes: 37o C. Adapted
from [12]
Mechanism
The thermosense organ in Desmodus rotundus
is situated between the central nose leaf and
a semicircular ring of pads. The folding between these two seperate tissue structures creates three distinct pits: two lateral and one
apical. (Figure 2.5) Each lateral pit faces 45o
away from the centerline of the bat and are approximately 1 mm wide and 1 mm deep. The
apical pit is directed up and forward from the
bat. The directionality of the pits and their
separation in space could allow directionality
of the radiation source. The bat is also able to
control the directionality of the pits, to some
extend, to allow the bat to angle them more
towards its prey. Under the skin, connective
tissue is the only thing at the floor of each pit.
This is unlike the nose leaf and pads, which
have tubular glands which end abaruptly at the
bottom of each pit as well as striated muscles
Evolution
2.6
Multiple Choice
2.7
Comprehensive
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