FEELING THE HEAT A locust can make a tasty morsel for a hungry predator, so being able to notice potentially dangerous looming objects and trigger the correct response could save a locust’s life. In locusts, a visual neuron called the descending contralateral movement detector (DCMD) spikes in response to looming objects and could therefore be the trigger for escape responses. Tomas Money and colleagues at Queen’s University in Canada knew that nervous systems in cold-blooded animals like locusts can be severely affected by temperature and can even fail at high temperatures. But the effects of very high temperature can be lessened if a creature has experienced a prior heat shock at a high, but sub-lethal, temperature. Money and his colleagues wondered if heat shockprotects the DCMD neuron from soaring temperatures. If it does, then the behaviours that are guided by this neuron should be unaffected in heat-shocked locusts, even when the going gets hot. To test this, the authors divided locusts ( Locusta migratoria ) into two groups: control animals and those that received a heat shock at 45°C for 3 h before experiments. Recording from the DCMD, the team explored how the neuron responded to looming objects when they kept the locusts at a range of temperatures from 25 to 45°C. As they boosted the temperature, they saw that the number ofspikes in control animals’ DCMD in response to a looming object decreased and the first spike occurred later. But in heat- shocked animals, the DCMD’s response stayed the same across temperatures , which suggests that the prior heat shock had indeed protected the DCMD. Looking more closely at the DCMD’s firing frequency during the early phase of a threatening object’s approach, they saw that spike rate decreased with temperature, but to a lesser degree in heat-shocked animals. However, in heat-shocked animals, the peak of the DCMD’s response – which occurs close to the time when an object would be expected to collide with the locust – is higher at 45°C than at 25°C, due to brief, high-frequency bursts ofspikes. This does not happen in control animals. Possibly, the higher peak firing rate in heat-shocked animals is a compensation for the lower firing rate earlier in the response, and the differences earlier in the response could cause different behavioural outcomes in control and heat- shocked animals. The properties of the DCMD neuron also change as the temperature rises: action potentials in DCMD diminish in height, although in heat-shocked animals action potentials are bigger than in controls. The membrane potential of the neuron is more hyperpolarized (more negative) in heat- shocked animals, which also affects how quickly the neuron can recover and transmit the next action potential. In effect, heat shock makes the action potentials in DCMD more robust. Another factor affected by heat shock was an afterdepolarisatio n (ADP); a rise in the membrane potential seen in the neuron after the action potential. This ADP occurred more frequently and was bigger in heat-shocked animals at all temperatures than in control animals. Although the authors did not investigate the nature of the ADP, in other animals it has been shown to make neurons more excitable, meaning that they are more likely to spike and elicit a response. A similar mechanism could be operating in the heat-shocked DCMD. The effect of heat shock on the properties and response of DCMD is important because it helps reliably maintain the neuron’s response in the face of high temperatures. This makes it more likely that DCMD will trigger an escape response if a looming object is detected. So, rather than being overwhelmed by an extreme heat wave, a locust might be less likely to end up as lunch. 10.1242/jeb.01725 Money, T. G. A., Anstey, M. L. and Robertson, R. M. (2005). Heat stress-mediated plasticity in a locust looming-sensiti ve visual interneuron.J. Neurophysiol. 93, 1908-1919. Laura Blackburn University of Cambridge [email protected]iv O u t s i d e J E B H E A T S H O C K Keeping track of the literature isn’t easy, so Outside JEB is a monthly feature that reports the most exciting developments in experimental biology . Shor t articles that have been selected and written by a team of active research scientists highlight the papers that JEB readers can’t afford to miss.
Transcript
8/3/2019 Heat Shock
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FEELING THE HEAT
A locust can make a tasty morsel for ahungry predator, so being able to noticepotentially dangerous looming objects andtrigger the correct response could save a
locust’s life. In locusts, a visual neuroncalled the descending contralateralmovement detector (DCMD) spikes inresponse to looming objects and couldtherefore be the trigger for escaperesponses. Tomas Money and colleagues atQueen’s University in Canada knew thatnervous systems in cold-blooded animalslike locusts can be severely affected bytemperature and can even fail at hightemperatures. But the effects of very hightemperature can be lessened if a creaturehas experienced a prior heat shock at ahigh, but sub-lethal, temperature. Moneyand his colleagues wondered if heat shock
protects the DCMD neuron from soaringtemperatures. If it does, then thebehaviours that are guided by this neuronshould be unaffected in heat-shockedlocusts, even when the going gets hot.
To test this, the authors divided locusts( Locusta migratoria) into two groups:control animals and those that received aheat shock at 45°C for 3 h beforeexperiments. Recording from the DCMD,the team explored how the neuronresponded to looming objects when theykept the locusts at a range of temperaturesfrom 25 to 45°C. As they boosted thetemperature, they saw that the number of
spikes in control animals’ DCMD inresponse to a looming object decreased andthe first spike occurred later. But in heat-shocked animals, the DCMD’s responsestayed the same across temperatures, whichsuggests that the prior heat shock hadindeed protected the DCMD.
Looking more closely at the DCMD’sfiring frequency during the early phase of athreatening object’s approach, they sawthat spike rate decreased with temperature,but to a lesser degree in heat-shocked
animals. However, in heat-shockedanimals, the peak of the DCMD’s response– which occurs close to the time when anobject would be expected to collide withthe locust – is higher at 45°C than at 25°C,due to brief, high-frequency bursts of spikes. This does not happen in controlanimals. Possibly, the higher peak firingrate in heat-shocked animals is acompensation for the lower firing rateearlier in the response, and the differencesearlier in the response could cause differentbehavioural outcomes in control and heat-shocked animals.
The properties of the DCMD neuron alsochange as the temperature rises: actionpotentials in DCMD diminish in height,although in heat-shocked animals actionpotentials are bigger than in controls. Themembrane potential of the neuron is morehyperpolarized (more negative) in heat-shocked animals, which also affects how
quickly the neuron can recover andtransmit the next action potential. In effect,heat shock makes the action potentials inDCMD more robust.
Another factor affected by heat shock wasan afterdepolarisation (ADP); a rise in themembrane potential seen in the neuronafter the action potential. This ADPoccurred more frequently and was biggerin heat-shocked animals at all temperaturesthan in control animals. Although theauthors did not investigate the nature of theADP, in other animals it has been shown tomake neurons more excitable, meaning that
they are more likely to spike and elicit aresponse. A similar mechanism could beoperating in the heat-shocked DCMD.
The effect of heat shock on the propertiesand response of DCMD is importantbecause it helps reliably maintain theneuron’s response in the face of hightemperatures. This makes it more likelythat DCMD will trigger an escape responseif a looming object is detected. So, ratherthan being overwhelmed by an extremeheat wave, a locust might be less likely toend up as lunch.
10.1242/jeb.01725
Money, T. G. A., Anstey, M. L. andRobertson, R. M. (2005). Heat stress-mediatedplasticity in a locust looming-sensitive visualinterneuron. J. Neurophysiol.93, 1908-1919.
Keeping track of the literatureisn’t easy, so Outside JEB is amonthly feature that reports themost exciting developments inexperimental biology. Shortarticles that have been selected
and written by a team of activeresearch scientists highlight thepapers that JEB readers can’tafford to miss.
8/3/2019 Heat Shock
http://slidepdf.com/reader/full/heat-shock 2/4
Outside Jv
PASS THE REMOTE
PLEASE
A goal of neuroscientists is to understandhow the brain produces behaviour. Thequestion of what is happening in the brain
during behaviour is quite a brain-teaser.Neuroscientists’ usual approach is topassively listen to brain activity in freelybehaving animals. But what if we couldactively excite a specific group of neuronsin an animal’s brain without using invasiveelectrodes? Lima and Miesenbock havedeveloped a method to do just that; theyhave worked out how to stimulate apopulation of specific neurons in a fruitfly’s brain by remote control.
To create their remote-controlled flies,Lima and Miesenbock geneticallyexpressed phototriggers in particular cells
in the central nervous system of the fruitfly, Drosophila. When they shone a lighton these flies, the phototrigger-expressingcells were excited, i.e. they fired actionpotentials. In other words, the researcherscould now stimulate a network of neuronsin a freely behaving fly and observe thebehavioural consequences, simply byilluminating the flies. To validate theirmethod, the authors expressed thephototriggers in a very simple circuit thattriggers a stereotypical behaviour with anall or nothing response. They chose thegiant fibre system, which is responsible fora fly’s typical escape manoeuvre: legextension, jumping and wing flapping.They found that flies that hadphototriggers expressed in giant fibreneurons exhibited these typical escaperesponses upon illumination. But whenthey illuminated flies that did not havephototriggers expressed in the giant fibreneurons, they saw that the flies didn’tperform an escape response. Lima andMiesenbock also demonstrated quitedramatically that the visual system’sresponse to illumination was not causingthe escape response: they shone a light ondecapitated flies and found that the
headless flies still initiated an escaperesponse.
Next, Lima and Miesenbock investigatedthe role of dopaminergic neurons in thecontrol of movement. Dopaminergicfunction is important for plannedmovement, and a loss of dopaminergicneurons leads to a Parkinsonian syndromeof impaired movement. The authors wishedto examine the behavioural consequence of an acute increase in dopaminergicsignalling. To do this, they expressed thephototriggers in flies’ dopaminergicneurons, illuminated the flies and watchedthe resulting flight patterns. Even thoughthe flies’ flight speed did not change afterillumination, they were more active,because the number of pauses betweenflight episodes and the length of thesepauses decreased. Before illumination, flieswould fly along the edge of the containerthey were held in and rarely ventured
through the centre. But when theresearchers illuminated the flies, they sawthat the insects began flying through thecentre, often in crisscrossing or loopedpatterns. Clearly, stimulating flies’dopaminergic neurons triggers morecomplex flight patterns, perhaps byinitiating more adventurous exploration of the central arena.
Identifying and stimulating functionallycircumscribed but anatomically dispersedpopulations of neurons in moving animalshas been difficult. Lima and Miesenbock’smethod might prove useful for the study of
any behaviour that is controlled by a givencircuit; i.e. most, if not all, behaviours.Courtship, mating, aggression, feeding,grooming, learning, sleep and wakefulness,and reward and punishment are just somepotential contenders that the authorspropose. Of course, this could also be aPhD supervisor’s dream: they would onlyneed to press a button to make theirstudents jump!
10.1242/jeb.01728
Lima, S. Q. and Miesenbock, G. (2005).Remote control of behavior through geneticallytargeted photostimulation of neurons. Cell 121,
high mortality rates that have not droppedover the past 40 years. This lack of advancement reflects the struggle to find asuitable model system to study the disease;current mammalian models used to studyacute renal failure have proved to beinadequate for a number of reasons.Surprisingly, zebrafish offer manyadvantages over the typical rat or mousemodel. Early larval zebrafish kidneyspossess the biological complexity inherentto kidneys of higher vertebrates. Unliketheir mammalian counterparts, zebrafishare translucent, facilitating microscopicobservation along the entire length of their
kidneys. Zebrafish tolerate manipulation ona molecular level, and their large numbersof offspring make them an important toolfor drug discovery and the generation of transgenic fish. Thus, zebrafish might be agood model system to study acute renalfailure. That is…if zebrafish can sufferfrom it in the first place.
To find out whether zebrafish can developacute renal failure, Hentschel, Bonventreand their team injected zebrafish embryoswith the antibiotic gentamicin and thecancer therapeutic cisplatin, which areknown to cause kidney damage in humans.But would they have the same effect inzebrafish? Sure enough, when the teamanalysed the kidney tissue of the treatedzebrafish embryos, they saw morphologicalchanges that are consistent with acute renalfailure. Zebrafish embryos treated withgentamicin or cisplatin also suffered fromsevere swelling in a time- and dose-dependent manner, reflecting an inability toregulate water, probably due to the loss of glomerular function.
To assess this potential kidney damage, theteam measured glomerular filtration rate in
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LOOK OUT BELOW
Did you know that there are ants thatactually jump from the trunks or branchesof tall trees? It’s easy enough to imagineants being knocked out of their arboreal
homes by heavy winds or peltingraindrops, but apparently certain species of canopy ant, such as Cephalotes atratus,voluntarily drop from great heights if approached by an imposing object. StephenYanoviak, Robert Dudley and MichaelKaspari recently reported good news forthose of us who might be walking undersuch trees: these ants are unlikely to landon us, or any other part of the understoreyfor that matter. Instead, ants of this speciesexhibit directed descent during free fall andsomehow generally manage to land on thetrunk of the tree from which they fellrather than hitting the ground.
To investigate the nature and extent of theants’ control during their descent, Yanoviak and colleagues dropped 120 individualworker ants from branches of their residenttrees and videotaped their fall trajectories.Falls typically consisted of three phases.First was a period of uncontrolled, verticalfree fall, second was a shift in bodypositioning, and third was a relatively steepglide back toward the trunk, regardless of the animal’s original orientation whendropped. The scientists used markings onindividuals to determine that they glideabdomen-first. A remarkable 85% actuallylanded on the trunk and, after a fewtumbles, managed to establish theirfooting. Moreover, within minutes, manyof these individuals had climbed back up tothe branch from which they had beendropped.
As is the case with most things in biology,size plays an important role here. Smallerants (inter- and intraspecifically) do betterthan larger ants; they fall a shorter distancebefore landing back on the trunk of the treefrom which they were dropped. Furtherexperiments in which the scientists blinded
the ants revealed a large drop-off in thenumber making it back to the tree during afall (10% vs 85%), suggesting theimportance of visual stimuli in locating thetrunk and controlling the direction of theglide.
The scientists also quantified severalgliding performance parameters byanalyzing videos of ants dropped within aflight arena near a fabric-covered verticalcolumn. In these trials, they found that theants’ average glide speeds were 4.3 m s–1
and glide angles averaged 75° (relative tothe horizontal). Although this angle issteep, it is far from vertical and reflects amuch better glide than what Yanoviak andhis colleagues calculated for an ant-shapedcylinder falling under similar airflowconditions (i.e. at a comparable Reynoldsnumber).
It turns out that not all tree-dwelling ant
species have (or use) this capacity fordirected aerial descent. Instead, thebehavior may be associated with groupsthat share certain traits, including arborealnests, branch-tip foraging and evolutionaryorigins in flooded habitats. A broadercomparative assessment of the distribution,control and mechanics of this glidingbehavior is sure to reveal intriguing results.For now, simply pause to reflect onnature’s brilliance in the form of winglessants being led by their rears to safety in thecanopies of tropical forests around theworld.
10.1242/jeb.01726
Yanoviak, S. P., Dudley, R. and Kaspari, M.(2005). Directed aerial descent in canopy ants.
the treated zebrafish embryos. This can beestimated by determining the excretion of asubstance that is only filtered at thekidney’s glomeruli and not significantlysecreted or reabsorbed by its tubules. Thus,they injected dextran or inulin, twosubstances that are filtered by the glomerulibut are neither secreted nor reabsorbed bykidney tubules, into zebrafishbloodstreams. They had labelled bothsubstances with a fluorescent dye. Todetermine whether the kidneys weresuccessfully filtering and excreting thefluorescently labelled substances, the teammonitored the decline in fluorescenceintensity over time. They measuredfluorescence intensity in zebrafish hearts bytaking fluorescent microscopy images of individual fish immediately after dextran orinulin injection and 1, 5 and 24 h later.They found that the rate of decline influorescence intensity was greatly reducedin gentamicin-injected fish, indicating that
their damaged kidneys were not excretingthe substances. The team observed a 75%and 67% reduction in dextran and inulinexcretion, respectively. They went on toinvestigate whether treatments usedsuccessfully in mammals with gentamicin-and cisplatin-induced kidney damagewould also be effective in zebrafish. Theyfound that, like in mammals, the aminoacid taurine prevents gentamicin-induceddamage and the compound Ucf-101prevents the effects of cisplatin inzebrafish.
And so, the old August Krogh/Claude
Bernard adage that there is a perfect animalsystem for every biological problem comesto mind in this case. Gentamicin- orcisplatin-injected larval zebrafish developrenal failure with characteristics typical of those in higher vertebrates and respond totreatments in the same manner as highervertebrates. This finding consolidates theirrole as valuable and unique models forstudying the pathophysiology of acuterenal failure and for establishing noveltherapies for use in humans. Who knew?
10.1242/jeb.01727
Hentschel, D. M., Park, K. M., Cilenti, L.,
Zervos, A. S., Drummond, I. and Bonventre,J. V. (2005). Acute renal failure in zebrafish: anovel system to study a complex disease. Am. J.Physiol. 288, F923-F929.
In energy metabolism, there are two meansof ATP production: glycolysis andoxidative phosphorylation in mitochondria.
The fact that mitochondria produce roughly15 times more ATP per mole of glucosethan glycolysis usually makes them theideal choice for ATP production. However,relying on mitochondrial metabolism hasits costs; mitochondria are the main sourceof reactive oxygen species (ROS),molecules that can attack DNA, lipids andproteins in cells. It is thought that theaccumulation of oxidative damage overtime is responsible for aging; this has beencalled the free radical theory of aging. Oneimplicit assumption of this theory is thatreducing ROS levels in cells should extendlifespan.
This is exactly what Samuel Schriner andcollaborators tested. They studied theeffect of overexpressing catalase, an ROS-removing enzyme, on lifespan in mice.Catalase is normally found inperoxisomes, organelles that contain
oxidative enzymes, where it converts theROS hydrogen peroxide (H2O2) to water.The scientific team generated three groupsof mice, either overexpressing catalase inperoxisomes (PCAT), the nucleus (NCAT)or the mitochondria (MCAT). They foundthat the PCAT and NCAT groups showed aslight increase in median lifespan butfound no increase in maximum lifespancompared with wild-type (WT) mice. Onthe other hand, the MCAT mice lived 20%longer than the WT cohort of mice. Itseems that removing ROS frommitochondria can extend a mouse’slifespan.
The team decided to take a closer look atthe MCAT mice; they compared thephysiological state of various organs duringaging between WT and MCAT mice bycarrying out a histopathology analysis.They noticed pronounced differences inhistopathology between WT and MCAT
old mice, notably in the heart. Indeed,many indicators of cardiac pathology wereelevated in WT mice compared withMCAT animals, indicating thatoverexpression of catalase in heartmitochondria affords protection againstage-related heart problems. To directlyassess whether the healthier hearts of MCAT mice were due to increasedprotection from ROS, the authors measuredthe activity of the mitochondrial enzymeaconitase, which is rapidly inactivated inthe presence of ROS. When the team addeda pulse of H2O2 to the mitochondria, theysaw that aconitase activity decreased
significantly in mitochondria from WTmice, whereas the drop was drasticallysmaller in mitochondria from MCAT mice.The team concluded that heartmitochondria from MCAT mice are moreresistant to oxidative stress than those fromWT mice.
Finally, to show conclusively that ROSlevels are lower in cells and mitochondriaof MCAT mice, the team measured thelevel of a marker of oxidative damage toDNA called 8-hydroxydeoxyguanosine (8-OHdG) in muscle and heart. They sawthat 8-OHdG increased with age inskeletal muscle of control animals but didnot increase in the MCAT group,indicating that MCAT mice indeedexperience less oxidative damage, in theirmuscles at least. However, none of themice hearts showed an age-related changein 8-OHdG levels. The team also noted atrend with age towards a smalleraccumulation of mitochondrial DNAdeletions, which are associated withoxidative damage, in skeletal muscle andheart of MCAT mice compared with WTanimals.
This study demonstrates that mitochondriaare at the heart of the aging process and
that limiting ROS production bymitochondria can extend lifespan. Giventhe negative correlation between standardmetabolic rate and aging, this study willprobably stimulate comparativephysiologists to identify key intrinsicdifferences in mitochondrial ROSmetabolism among species.
10.1242/jeb.01729
Schriner, S. E., Linford, N. J., Martin, G. M.,
Treuting, P., Ogburn, C. E., Emond, M.,Coskun, P. E., Ladiges, W., Wolf, N., VanRemmen, H. et al. (2005). Extension of murinelifespan by overexpression of catalase targeted to
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