Scribd Logo
Upload

Welcome to Scribd!

  • Chapter 11

    Uploaded by

    Wilco Rave
    18 views26 pages

    Original Title

    Chapter11

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Report this Document

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    18 views26 pages

    Chapter 11

    Uploaded by

    Wilco Rave

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 26
    sous ld epigraph at the tar of this chapter rcogies at progress in science often sn nevis abot com rmonplace abject Hisidea applies brllanly tthe iscvery of bilogicl pacemakers. Although the speach ssmatienocleus ofthe marnallan hypthslamas hed been rote since the ealy 180 nothing wae known about i function ‘beyond idle speculation, Only half centr ago afew isolated cen ns ‘ste apologetaly vice ther views ta undiscovered intemal bio logical ners played ey sole in regulating hythmic activity ofa wie variety of animals and plants The prompt reply of most of the scientiicommunity was Shove mean teal cock” ‘One ofthe fist ving cack tobe found was inthe optic lobes of inset an for mols like Bulls, eal inthe eyes. Fguraivey new tyes have been opened in meteoric traetry of dscovery based on Te ideas and fecnigues, Chapter opens with a consideration of human cla evottion and the eonsequent awareness ofboth spatial i temporal organization. The api progres ofthe fel of ehroncbi ‘logy inthe past decade i discussed brie, and the difcly of acu rately projecting the course of chroncbiology research findings in the ature mentioned Te significance of biologi timing in our present day wodd is portrayed in sik themes emphasizing recent advancesin toncbiology earch, Looking Forward ‘The rel voyage of discovery consis landscapes but i haing new eyes. Mave! Proust ts notin seeking new Introduction: Accurate Predictions about the Future of Chronobiology Are Hard to Make" A sleace back at the history of human interes in timekeeping wil sharpen the focus of any forward projectonses=nccsir PE HUMAN TEORALSELEAWARERES. Ths ook began is journey wt lao back 5:00 years got the important ascheologcl stat Nemgenge ln. The ‘cebu st ater 3 meting tan undergo cpp Ono Suro on te dy ofthe winter solace dose us ligne nth to tar! Slow a moteo sumo lust cyt Panioy human cat ony guess the sgntcanes of the ight nystcaly tucking te stone, bute wrk con ting the monument songs tt hy stcant eel as were involved: Even moe sigan was the poco gate stone monument be ingat Sonchenge Starting aout 500 yer ge sed contnung overs period of lost 2.50 year a good deal comunity eoegy mest hve been ced ‘ine ated to moving the pac stones ting hemi pein, andthe carping othe cla and lar eens mst ave orn contre The ving oc hd these events understood i te emework of 9 sey development in nan evlason hat had begun out mlion yrs eee ‘Advanced ung copes an awareness wee emerging ty ou te {Gemer restraint osteo igly programmed betula of nxt ‘mun arimals-Atcome poi aly Muna sve he apa fo ewig the Scives inate rein pat petent and futur That nique endowment wn ior aon he cata evlton ht wo fallow Chay evident adden 360 chapter 14 now hun neve nine measurement devices an thei appleation te human everyday practi! fe, 9 wel asepritua ie “Tue Rave 9° HUMAN CULTURAL EVOLLION, The mi Tenn long evolution inhuman understanding of bio: logial timekeeping is cogent relevant to predictions “ofdeelopments hat the nest century might bring 0 the field af chronabology. The gradsally emerging tundeaaoding ofthe copii and adaptveness of ological neheoping as not beens state progreation “Dente the rate of increas of human nella awate- nessa beon neither liner nor unforr, Two fren, Factors ave been a wore Fst, uman cultural evolu tion proceeds in general at an ever-increasing fate Second, bsliant splice advances re nares nto longing platens “Te lgttie creat in the te of cull change ls analoges othe opening and page tuning of huge booksuchas an unabridged dictionary When the book ‘sopened the extent ofthe vas compendlutn of word fled pages becomes evident Each page sande ir ‘ively ors major advance in Pman inlet ine Sanding The page were turned owl st fit, when Snowe sent prceses wos minima nd most econ ere base om supertiion. Son however the te of tuning quicened, ene concep pened unex ected orzo for exploration and eventual Be ” = RGURE 11 Fn epi ft iro aman alte 2 fcr preitng re pros in ‘rondo. A) The taming pe sage ep Seber yanin tet tl ee iecoedrefscoveas tat ut neces 215 could no longer tum the pags fast enough o beep 1p withthe pace of centile progress. Now the ever increasing tempo of tring causes the pages to spn past and dissolve to abe Figure I-14) The proces ‘stated conc bythe exon inthe tel min: ber of site paper published and inte incre thenumbar of level of eperaion af cain docs tes rm the sata an court levee down fo the ‘molec level. ‘The second factor, the alternation of advances ad platens, resembles the impact ofa a, smoath stone kiMally patched acros the glassy smooth eater of [ake The stone sips actly cron he surface. Each time touches th surface ephemeral the one gener ates a ring of ripples Ut fan out and serach pre Cecing ng ses Figure 1.1) Asa metaphor human fulturlevoltion, etch tochdoven and new Hing of ‘pending ripper sles maor advance. ‘Otten in fhe history of nce, an acance the de novo dacavery of anew scenic concep ot ne fol The bling af simple microscope, hardy mre than 1 magnifying gles, by the Dutchman Antoni van Leeuvrenhoek in the ate 1600s changed the course of biotogy Similarly, Chatles Darwin's bea tay in the {Galapagos Islands, just | month long, gave rise tos ‘moriumentl boo On th Org of Specs by Nar ‘Sco. The timely quote the beginning of his chap terby Mare Prout capores thee dese el CCHRONOSIOLOGY KNOWLEDGE. Certainly one of the touchdowns ofthe skipping stone fr ehtonobilogy truce recognition of itertal ming spect. Clarke nd calendars ere a pervasive force negli pac tally every aspect ofthe rhythmic ef ealy human fulton Whether ery bseretions were trl St omical or merely antrolgicl i anyone's guess, [Although the tru rigins of emporal self arareness ‘all never be known, sme lies canbe found Many instances ofthe adeptivencse of temporal pro ramming undoubtedly were apparent tea tans |ansguity Thepithy quotes hat start he chapters and ‘other parts ofthis bok elt powertuly the interest of Fhamane omall walks fife inthe neil atid eve ceding march of ine ltr weote 200 eats 0, “Times the wisest of ecurslos"Trom Chapter 2 ome snanclent proverb that alot cna prettes writen Tanguoge Time and tide wath for no one” was Fest, recorded in one ofthe eats! European weten ecards etsh bok of provers, butt surly had bee handed ‘done by word of month for millennia peso. No oe ‘could have imagined st Newgrange what Smiles ‘would bang om the scientific sone For that mate, no (ne could have foreseen what century of rages ‘would produce in understanding eral ine 360 Chapter 1 ‘ew human intrest tne measurement devies and ‘ir appliaton to human everyday practic Ife, a= vel asspiinal ie "HE RATE OF HUMAN CULTURAL EVOLUTION, The sil Tennlalong evolution in human understanding of bo Toglal imekeeping cogently relevant to predictions of devslopment hatte next cenary might Bring to ‘he field of chronobioiogy The gradually emerging ‘understanding o the complet and daptivenes of biological emakeeing has not been asia progression because the rl of ingeaeof nan intel aware ‘ess beon nether inen noe urorn. Two different factors have been t work Fist, human cultural evel Hon proceds in general at an everncreasing vate. Second, rian stepike advances are inert nto ongoing platens “The logan rere inthe ate of ural change Is analogous to the opening and pge turing of ge book such san unabridged dictonry, When the bok 'Sopened the extentl the vast compendium af word filles pages becomesevdent. Each page sand figure tively fora majr advance a human intolectual under. Sanding. The pages were frme slowly a fist, when owledge of sete processes wae minimal nd mae dais were based an persion Soon, hoses he ‘ale of ung quickeed as new concep opened we ected horizons for eplration, and eventual the Bi w FIGURE 141 Figura depiction ofthe to net of ‘Roman ele 3 fat preci uae proges ‘hnesinogy. (4) Tatung geo sree pe Sarin peal rhs atl ang oedema Secorretiarautincdseaicangs 27 could no longer tur the pages fast enough oben {ip with the pace af selene progress Now the ever Inereasg tempo of uring ruses the poges tpn pst nd dissolve into a Blur (Figure 1L.1A) The proces ‘strated concretely by the elation the eval ns ber of sient papers published an in the nce in ‘henunbereflete of peratin of ccaian cc i ie rom the scl and corurityeveis down ote ‘molecu evel "The second factor, the alienation of advances and plateaus, resembles the impact ofa fa, sath stone haltaly pitched across the glassy emath wate ofa lake. Th stone skips graceful across the suc. Each timeit touches the Surface ephemeral estore genet ats ering of eppes tat fanout and neract ith pe ‘xing eng ss (Figure 1B) Asa metaphor oruman Cultural evolution each touchdown and new rng of ‘expanding ripples sigs amar advance. ‘Often inte istry of scnce, an advance the de novo carey ofa new sciefe concept ara net. The bung ofa simple micescape, herd more tha «2 magnying glass, by the Dutchman Antoni van Leeutemhoek in te ate 1680 changes the course of Dlology Simalarly, Charles Darin’ bre sty in the Galapagos Islands, just I month lng, gave rise fo hs ‘monumental Book On the Cri of Speis by Natural Slt, The imely quote atthe begining of his chap ter by Marcel Proust captures thse ideas wel CtoNowiouocy xNOWt EDGE. Certainly one of the touchdowns ofthe skipping stone for chronobialogy vaste recognition of inerral ning pact. Clocks ed calendars were a pervasive fori eeulating prac ‘really every aspect ofthe hic ef early human alors Whether eat observations were aly astro fomical or merely astrological ie anyone's gues, “Although the te origins o temporal sell-ateness ‘will never be now, some cues can Be fin Many instances a the aptvees of temporal pr gramming undoabedly were apparent oer humane {antiquity The pithy quotes tsar the chapters ane ‘other pats of ts bok rele powerflly the terest oF ‘humans romall walks of Mein the inevible apd eve nding mach of time. Patch wrote 200 gests go, “Tims the wisest of counselors From Caper 2cores anancen prove that slot certainly poste writen Tanguage Time and te wateth foro one” was ist recoded non of tees! European writen sors ‘Bach book provers, bt tsurly had been ane ‘down by wort of mouth for lle previously Noone ould have imagined at Newgrange whats millennia ‘wold bring on he scientific scene For hat ates ‘one could ave foreseen want 3 century of progress ‘would produce in understanding intemal ine Awareness of the adaptive importance 0 bolo «al timing as grown rapidly inthe past cecade™ The pac of discovery in the ld of const ology has See) aid inept decade Sy te progres are accolades bythe pretgtussenaicjout ‘al Since Read each week by about half lion enti it one of the foremost fous in the worl for Feporting new scenic advances For the past ew yes Scbr has feature an article at yearend that Sims to predit thes elds that will eke slenc Inaines tn he coming yea nd ciqus the seuraey the preceding year's choices, An acompeny ing ai ‘aime tats “Bet forcating ino ena cone here ‘we ate whether ou erst al was clue clear, second pat of te anal Scr survey mongzes aout ine noteworthy scene discoveries “hat rans form our ideas about the natural world andalo oe, Potential benefis to society” Scene applauded beak Sheoughs in chronobiclogy in ee of te pasts yor In December 197 the benkthrough diseover ented the cloning of everl new ctedian genes eluding white clr Tand-2 im Newsy, and Clot in mice & gene similar oer was as found in mice and hare NNotonly was the or gene stv inthe bain poomaer ofthe tru iy but alo many pars fthe B's by a December 198, the ist unneupsnteswesawaned for further genetic advances in chronobioogy At the ‘los of 20 the el of chonobiclogy was ognized by Science for the loeaiation of previously unknown ‘manaalian econ rena ganglion photoreceptors “Te premier association for tose who sy Bolg teal locks inthe United Sates ithe Soy for esearch on Biclogial Rhythms, and its itrary vole bo he. nt communty ofthe wold the out of logit ‘Rhytons TBR: Se igre 113in Chapter), Ont ce slon ofthe 1998 anrwuncement in ecu, TBR Eaton Fra W. Turk of Noathwestrn University wrt an et. ‘oral entitled "A remarkable year for clocks sed on many yestvofinrdlsipinary each” He ve that Sergent” hae Sept nul 9 lin Jats een) shore the seme tekaopng goer and prin sre ng ena Coc unc oSoea bckhoops nese 28 yn Whe te dg edian bologte the sreption lat sin Weinad enya iene tng een ‘errs she he ndings the elt of opal yeh st cries eine tnd mechan levels soar oe al ing Looking omard 361 gals. What ote unexpected erp, wi brdleeeed a esas ‘poses besitghe te made? Turek’ words serve bath aan inspiration fo the future and aba waring abou the dangers of making predictions about progeee too far into the fture Chapter twill make no attempt to peeiet what the tovety-second or went 2rd entry, much es the ‘hit, wll ring Instead it wil extend some of he breakthrough ideas develope inthe proceeding ten chapters into lel rection othe newt decade ‘Sc forward-looking themes have been chosen to close Chronobiology: Biological Timekeeping!™==68 The preceding section emphasize the dic of pre- dicting scientific progress aver long ime spars More realistic estimates ean be made for shorter peri Rather than pedi he course ofthe whole ceo gy fla sper goal hasbeen chosen. From a nl. td of possbie topics themes wil be highlighted {a5 came portaits of important recent breakthrough {vents in thronobiology that may help channel the ‘ietions of cleadian esa inthe next decade 1Progress in sleep-wake reserch and its ppl ‘ion tohuman welfze 2:The ws frontman vrtsbrte models te dia sleep research Growing use of ivetbrate model species for t= ‘dian molecular esearch “Peripheral pacemakers in amas 5-Use of SCN Clot mutant chimera in understand ing ciadian pacemaker mechanisms 6 The consequences of ecosystem degradation rl tive to entrainment of ccdian systems ‘Theme 1: Sleep Research in Humans Is an Important Area for Future Study=terensr ome ‘Numerous theories postulate the function and mechanism of sleepin humans Because slep fo most humans san cbvious and pr sonally intresting spect ofthe cada ck gees tons bout il larly bes focus of future cach ‘The opi athe funeton athe mechan of sep ih humans is sil debate, although a number of ports sivetheois hve bon propose As common sear fis; mos theories propose» recovery function fer Slee. The behavioral ares fe inelee roonged 362 Chupter 11 minbiiy nresed arousal hes and homeost te dive lo nake up ont seep I mere energy conserva tion were the ony requirement, simple immebity (would suffi: Eve as spparet the vali of ea ingawanencs ofthe environment ithe pape of sep twee simply fo educe metabolic ates. fot, educed ‘Reponsiveress othe environment and the oveehel {ng ned tose con be highly mladapsive n some st thtions Aseping abt in an open field ora drowsy human ding ears ebviously an individual at esk ‘Shep mayafect somatic as wel as cetal nervous system (CRS) function, bt the eaborte nature of mul ple statesof mammalian seep has diets stteton ICCNS ists Several theories prope tat neural fase tion enhanced by sleprelted neural plasty Inthe lt promotion of lng term memory consliation Alring sep could optimize adaptation toa changing ‘vitonmest Inthe developing organism seep may foster neue maturation In an aging arma or one b> jecto neural malfunctions, sleep may promote healing ‘rat least educe the damage of dsese au, and ‘degenerative processes As part ofthe mechani for neural restoration, ep may speccly regulate ene 1 and mesbolim in pearal moses [9 Us Way eu Tons may bs protected rm energy depletion dt the toxic eects of high rates of metabolism or Muctuating ‘en avast during an organisms active period ‘Sleep research and circadian research are Increasingly collaborative ‘Uni abou 1985 intercon between the lep and c= ‘dian ehyt msn commis was que mal ‘Sleep divorders such as insomnia, or the more severe sffoive sep caordrs See Chapter 10), were treated ty physickne ss medi problems Few Grxdan pay ‘logit del with humans as esearch subject, prime ‘ily Becus ofthe age cost and ethic comsertons. ‘Another reason forthe lack of verap of he lee aed ‘readian feds wae their to ferent vies of slep. ‘Scientists nthe slop eld bleved atthe clock ust, {old the onanism hen tsloep but sad nothing ela fet fincton or he drive sleep, whl cicada tise comidered the slep-ivake cyte ust anh. output eth dock, meri anaogousto feng body ‘Emperatur, or hormone hythms: As 3 resulkcomse: ton between the wo disciplines of human sleep aed ‘Sra hyths were very its “The oxtogk for rewarding collaborations ofthe two fils ine uta promising. A growing numberof pint crcadian-sleep sot programs have Been held "tional and neato stings, Sergi inter: ‘chor of he vo are steed with increasing ‘quency ty the view that circadian rhythms, the Sleep-wate cyte, and the metabolic Budget ofthe human body have al coevolved since the begining of leon this panet Chronic pata slep los isa major health issue In indusiniaized countries: Nolonger do mos physicians cof atthe ide of inal ‘xlminstrtion of pharmaceutical drug ep thea ‘rlighttentment for afectve disorders (se Chapt 10) The reasons eae Seep defi affects milionsof prope: At least of people over 65 years of ge, ft Instance, have sleep problems severe enough to restt Inlasp delice, anda maj of nonprescription pa ‘maceticls bought bythe elderly ae for coping with "Sleep problems Sleep deft haw major imps oe ‘optimal aly pertormance at home and on the jb Chronic seep fs is zety relate to Industrial and Highway acetates In adon sleep deficency tas ‘aor overtones for longterm chronic ealth problems Slep duration decir n America. Avetage Srp duration has dressed snc 190 from 3 for ads 275i 1975 Several factors ae neo Since 989, be Smountof me spent at work has increase by 158) pet Year A2 heat shift work, and moonlighting bs Sr all n par o blame. The insatiable demand of ‘Americana for “the goo Me” has also reduced slxp time, Grater income, rete recreational opperi, Sr incre television watcng have changed the ce ‘salty from the pal arm ie yal omits {in 10 tothe busting neresanging,peripatee urtan lsh of the een fst contr. ‘One convincing satis ofthe detent effet of sleep diet on performance comes fom recording shortterm memory lapses clave to normal Function, ‘Seep dee and slep exovery periods. Without a dou, opnive function seriously mpaied by soe detest ‘hough some let seen in young ad, he eece “lrupin nthe elder gives x guieting view fete future, given our aging population. ‘state of le debt in young adult associated swith endocrine and metabolic aeration Batre simr tothoreobrered sy normal aging The changes inlnde ocresse glucose tolerance, nteased evening crtsl levels, and increased sympathetic tone. Chronic sleep Tees am increasingly common condition in nds {aed countries This sleep lose ikely to nerease the Severity of widespread agerelte chronic conditions Sch as best, diabetes sd hypertension ‘Sloop deficit aggravates many health conditions fhe elder acts Normal sleepin most human cultures entails 2 ui ‘modal period of consolidate sleep larting 8-9 hears triha regula predictable secesion of cyeling stages of REM and non REM sep. Sleep canbe measured ty ‘tecoencepalogaphy (gure 24) which portage the characteristic balwate patterns ofthe specie sleep tages (Figure 11.28) Generally the temperate ‘elegy ne wih Se sepevake fe ts rung thatthe tompertae minum fal shorty ster the milo te sep perio. With aging some of te charac he ep le change ad a ous pahologs rl The dency oer eae) Sy mapping dure dy ara elo ge nce Sy dep astncton Avis ce ay el haan spill rer fom simple fatigue to major impact on any physiological hinction and media conitons he EARS 1. Boerner soos shal Aelel 4 anergy FIGURE 12 Summary of he myographic encephao- (fap nd octane of ie chal epee (GySampleshor rm EEC cong re an wana thsi que eeteecalf an eae sn ectDigy Aalndg Unony Deore be Locking rored 365 Maes onion Fons As lifespan increases in industrialized countries, age-lated sep problems becomes malts o ational ‘oncetn. Age srturing in the United ists hes ‘hanged dramatialy inthe pst century because of bet teeth care and he resin inease in anges A comparison o logevty in 1900 and 200 tte he fis in ie span (gure 1.) Today many elder dividuals continue to enjoy an active physical and 0. ‘ial ife well int ther sand even Ss, bu sloop de Feit probleme ae widerpeead in te deny These sleep-wake disorders jeopardize good phystal sr mental health. Chronic sleep deficit versely aferts memory, peeforarcecopabiiti,an! the genera ous $y of life Althoughreserch on slgpcontinies actively ‘ot human subjects many consis knit progress, se Chien 11 Limi on lep research n humans wil ead peta to the we of al model inthe Soop research with humans isexpensve and etait ‘nary etal considerations. Coneueny aernave ‘dent mdes re very desable Inthe ure, dens ‘wll probably supplant human subjects for many ‘earth projets, peril for experimen approace ‘Sin te nborstoy Some den adele arsed in Tepiptine ‘The cicadian Clack mutant mouse. or examples roving a Nighy valuable model or human esearch Excel tant defective noe ta cic dan gene its been used o tease apart the ccd ompenents rom the lep-wae ce components. n thehomenygous ste, individuals ill have very long fe uring periods in DD. The fers deterio rate gradual i sey tnihy The gee fed Sol th SCN rout facons in ara As {res the mutant motte oes many opporanies for examining gene contol of sep One eample con ‘cerns the role ofthe SCN, which hs been vey onto ‘erin mammals nciding humans ite sown bout the consoldation of sleep and we ates by the section of a ara sgulby the SCN. acs alenist nothing isknown yet about the mecanisn ‘fsignling The extent which te ccadon sytem insences sep recovery in humans ilo trio, ‘Onerepresentntve dataset il be presented cre plly he many new facts obtained rom dep studies fhe Clock mutant sows. ‘When homexygous lo mice ae subjected to stress by physi restraint fatigue induce, Verous mens ter of slp cn be coded in the saben! er period Meosiemet of the ttl mount ole, ‘ert REM sep and REM sheep nthe 1 dk peo teas igh sige diferenes etween wise snd omorygousaythmic mutant mice igure 1.9). say adoro im ‘Sep Nona — RB FIGURE 114 Relative etfect of restraint stesso deep ‘covery in uletgpe cond mice and Clock mean ce (Gouna of anim end eck) ‘summary of fetus of the erehythic mice ative to wildtype contol indicated intesed wakefulness decreased ampltude ofthe sleep-wake cycle, snd reduced sleep covery after sleep deprivation OF The next theme will elaborate other ways to lesen shout sleepin humans, Comparative studies of le processes In noshuman Vertebrates promise to give inay sighs np he pigepestic crt span ‘Theme 2: Wile, Free-Living Vertebrate Species Are Being Used to Understand the Circadian Basis of Sleep">4asssssa97 ‘Studies of nonhuman vertebrate species, especially wild mammals and birds, are a recent ‘dynamic development ia sleep research ‘CHALLENGES. Research has emphasized human sleep tunel very recent for good reasons Inhumans en Tatonary development of sep has reached ts pina le Generally 2 moda seep patter coining with the hours of darkness is preset, and 3 dstincive ‘fling between stages of sleep over a discret 809 petiod per day curs, The behavioral stapes correate ‘wel with brain ard muscle recoding nation Seep Intensity and recovery fave Ben eatively ety todo tment in humans I contrast sleep patems ae ore ‘complex and more dificult reer and interpre in ‘nonuran verterates, and the very existence se fas Been questioned for mas invercoates, (Only ently nave the ivaluale cpportriis for ‘logical and phrsologialreseueh in nonhuman vet lebrate species been recognized and. aggressively explore. Freeliving wild species, of course, present Some clssdvantaes a research Wi crestre a ge ‘aly very scene during the vuierable qulescet est ‘rsieep period. They ae sen dfn fo capture and they may show many sleep atlats during observation and recordings in captivity Neverdheles 3 singe of enthusiasm for shes using wild species promiser "api progress nthe near fut, Two tends ied a laying functions of lep ane evident a phylogenetic pproach and an elogil appresch, FHLOGENETIC APPROACHES The thrust ofthe compar ative phylogenete approach ft record Rndamentl Sleep properties fey specs ors many classes ad ‘eders of mama's brand lover vertebrates os po Sibi The hope sto reves the fist appearance o seep ropes from spl to complex nerd a gin abe ferhandle onthe mechanism o sleep (Table 11.1). A potential pial tat a unetion involving multiple Looking Forwaed 368 currence of sleep and sleeplice properties invertebrate groups etwvora | : a sequence but ather an interwoven web fetes and ‘mechanisms that ay be difcl foave par ‘Comparative gusto about spn vertbrses ave snnacnd s surprising numberof setts Ass rol, Slep fs eel ee exine in ae oe spe of ‘most marlin and avian odes les ar 4) In Uhecomparnve say seep mectaroms and functors, several fundamental properties Ravn boo coelseed Betavoa sop is rlatively ey © dram. One ep oftehavioral ses concen the dtm step tl. "ve tothe environmental light-dark le, Other atures ae physolgial, ncuding total REM and no REM Sleep, the intensity of seep and slae every a the ‘ccuranc fhe phenomenon uierspesep ‘Several generalizations abot lp stages fr ma masa lower verrates ae now posible Incontast ‘ohumars mast oer vertebrates dent haves tong Iy amid conolite period of dep Intend many Fave complex multiphase seep paterns Even i they aeighlynocural or dupa ia hae aeity patter, ‘hey may alternate brief sleep and iske periods "soughout the inactive peri of he day. Beviorl sleep, long with» clear diferencia the BEG between Slep and wale stats is evident inal vertebrate see from reptiles to mammals nd f wen even in fee species of amphibins ahd Tish Slow scave slp is well developed inbirds and mammals. REM seep ‘Sdeveloped in most mama ee bids Sues in mammalshavenat = shown correstonsbetween sip GDP parameters and body tamper, Mena Preeneothibematen orien Naaupie ‘lange proportion of there: Rant searth hs invlved the pegs: Cares neti distbution of REM seep Pas mammals becans thst the nay Iceprwakesyciehar been consid Anns edokertieorhigherversbais, Coneans Data from numerous species have allowed phylogenetic comparisons Amount ot EM sep in several groups of mammals between mammal groupe. An overlap inthe total ‘mount of REM steps apparent across oder tng, from Oh toa mania of 80 8 (able 112) Howevee ‘more than 100% variation occurs within particu ‘fers REM sleep has been dcumented inal mam ‘als except opine, though the data about dolphin tay be an artifact of the recording method, which ‘equi econting a atined doh, Othe aceans [hve very low amounts of REM sleep, and also very stall mounts of tal sleep, Srila te reported Ick OT REM sleepin the echidna, a manoteme, may be 30 rac The chien ete’ sleep properties diferent from typial cording in other mammals, which mae itvrpretation of he data ambiguous “The sue of REM sleep in echidna is important in light of recent careful studies of the only other _monotteme the duckie platypus In this wns Species, the total quit time resembling sip ranged From 58 108, withsleep senting REM costing most ofthe sep period (Figure 1.5) The motivation forintense tudo the monotemes sn the question of evolutionary origin ofthe fundamental properties of Slee. Exly atoms and phylblogal studs ofthe bran suggested thatthe pons wos prylogentcly an ld pat of the rain, ard that wa alsa vil pat of Einpe)___WE dep umber aout per 240) Panpus —__ SB80(ofetal Bh ut sate /dey) Garidanese) 1332 Cate gee ig wz Daphin oo “Sie Dom HS 366 Chapter tt OM i on sow fee FIGURENS Sleep stage sracurin the dace pp eS ee one stevollge RES REN step, igh volnge: ran Sge el REM sleep These faci anged forth nl eveltion of [REM sleep. Argument gant histheory ar he oc ‘ee of vivid dreams infurans, suggesting neo fino! REM sleep. Evidence forthe ne derivation of REM seep also comes fom te lick of cecurence in reptiles and ampiban. ECOLOGICAL APROACHES Iv MAMMALS, The second trend her boon an ecological perspective that covers Feld observation ad abortory ecrding plus expe ‘enlton floras many species as possible, Close mem bers of taxonomic group with extreme ecology and behavior patterns have been emphasized. Presumably the coreaton of sleep characteristic with ecological Ibtt wl goes beter ander ofthe funtion (Of sleep. Mach emphasis hasbeen paced on mam malian REM sleep asthe measurement paramett ‘Several consistent ecological coreations ae seen with expecta mammal REM sleep, General the ‘mount of REM sleep pall the amount of rer-EM sleep, and the aout of REM soep tm x correlated ‘with oa sleep time Ahighcoreation is also seen between non REM sleep time or total seep time and body sie. The correlation ssegative: the larger the nial theese. ‘Another correlation cancers the relationship of mount of REM sas in tamale ative to the sect ‘iy ofthe sleep se Ths link reflects the ecology of» Species, especialy predator-prey sats. The more Sure the seep sites he grenter the amount of REM tls that shown. Consequently predators de> tiesleepers ith concealed sleep tes can apparently for extended periods a sleep Lions re the prover Bat slepers ofthe animal Kingdom, ang they exhibit Tange amounts of total swell es REM, slep Sina, ost nts, including tigers and domestic house eat Ive lange aroun total and REM sep. In cons, late wit unprotected sleep ses, such scat, {ales ander ngehersvotes have ray ow noun tol sep nloding REM sep. ‘Apes cori la fond fe rain shelve aroun of REM sp td the ops hp icsarlon ail nly wich ar born no ‘evan pen uch asnampa exh ltely Inge amounts of REM slp The amount of REM sloop decree inthe aut bur sil high compared ost alti Sage of ay priate, 0 ge ‘Stamunt of feMalep 13 pr dy Acre une Spas theonl mary wh pr day No cretion abe oud ete REM apa nan te, Gibran tbody wag or chennai ype el. theta the dy nightcle. AIS. Bie contact the mammalian ecologic cor Tetons Allbils ecb REM sep. The cycling how ver is simpler than in higher mammals, AS with ‘onprinete mamas substges of ner-REM sleep can ot be distinguished. Compared to mammal, bids in feneral ave small Many ae predators Most predatory Binds ave day-active and sor secure sleeping paces tinder cover of darkness. The great maori of species have extremely lta young hat hatch froma Vl femble egg Exceptions are the precocial ground-neat Ing species, suet as most weterfow! and almost al shocbids ful, end tems (nal these counts birds might be expect 0 show lage amounts of REM sep, but the data come a2 prise. Most birds average les than 30 mites of RENE Elssp per lay. Even more surprining i the fat hat he largest bird show the greatest mount of REM sleep. ‘The generalizations from mammals are dameticlly ‘pposte to bicd rls, “Another cortelation concerns the relstonship of un ‘emispheri sleep with the neo for constant igance Doth during daytime and nigtime. A few spaces of mmanimals ang birds can seep with one brain et [phere while the other hemisphere maintain a vga Siete Without s doubt, the ecological function of un Fremisphese sleep ls protction, because occurs pr ‘any amas wih specie sep vigilance needs Best knw ofthese species are cetaceans sich dol pins During pris of rest dolphins may keep one je closed the side opponte the awake herasphere Simla rests have been reported in pinnepeds suc = seals Most ofthe opin exch us involved behav ioral caertons, Some doubt exist bout the dat on jt poston cause of problems in cording it whi ‘dlpins are actively swimming, Excelent new data on unihemisphere slow-wave slspandine stato eyes ey recy bce {aloe rhe elugy or whe wale Ths epecs S higharaicothed whole wth a sumber ef orem iehaviors and physiologic! adaptations for stvving ny waters inctding dhe sity to ep underates forentended periods of tine witout sounding othe Stace for beating Eye poston, swimming and bran rave active sinlaneouny corded ver apenod oft days For the ot pay the eu ‘Support hypetieioeye sure coated with ‘tal sep of te opposte brain hemisphere igure 316, An overall rlatonship tween the epg hem Sphere and eyelid prion won observed bt rap changes ineyelid poston were ot lvays flowed oy imme changes in EEC Eye poston and EEG were highly conelated overlong petodset time, but thy could beirdependen ove short eros of ie sting Jess than Iminute. This capability alows bot begs ‘whales ad doin to bresthe sep sri, and eo tocther environment imulaneousy Theat ray be ‘eryimporan fora species hat must constantly aoe Swinmingmoversrts to main ase positon int hydiodyramialy changing envionment Sil observations of uninmpheislep have ‘ben madein agua birs Tac eres re data fom soil bids such as ducks in flocks Like ‘ciaceans, ducks can apparerty keep oe eye aig ‘wil tepng with the opposte ban hemisphere. & Scanning ack in beavielcep potion canst ot threatening visual stimuli action oa scond Date supp the hype ye of eepng Thetop t ecto fr he att Seyi Re teed Lit jettmalac Operon Tee is the ES forthe ighthanse kee phar EEG wae st bots Ear samn el 2002) Looking Forward 367 ‘snantipredator adaptation. Bis more exposed ope dation use sucha sep peter more cen han bes the nse of group and the eye that stays open mene Istheone facing the dtsideo the group. Although birds and wild mammals re good altematives 0 humans for circadian studies such {3 sleep, other even simpler models may be necessary in future circadian research Extensive studies ofthe CNS of mammals ave yee 4 relatively detaied understanding ofthe sratomicl structures regulating sloop and other ceadan fact Much salso known abut systemic moral an eta boli fairs that infsene sats of arouse an sot thensurotansmittersytems invelved instep oe ig ‘ance. A wel-oganize aay’ of changes outs in oe ta firing and in peural networks. The electrophysiooy, fea changes that accompany normal dally changes ft Consciousness have also been extensively tavesigatd. However the denifcation of single gene cela fo slp, sich 25 he gee relating advanced sep pse ‘Syndrome (ASPS), a aut recent even (ove Chayer 10) Even though ithas ben ented, the role of is gene in normal sleep-wake regulation i not under Sood. Thus, the molecular Bais of sleep fegulation remains rer, "The aplistion of moe iol of molecu bil ty foan aray of animal models stone favors the se [simple mvs uch a the nematode or at Since the genetes ofthese species are eatively wellknown, genetic engineering approaches ae pose In ad tion, the ental nervous systems of these organisns, patclaly rit hes ate atively simple noone Fanetions in the comples bis of Vererats se mich ‘more dficul to stody For example the reticular ‘enrol the rum ran extend throug the ene fore of the brain and regulates level vigilane nd the sleep-wake cycle part of the ceil system called the reticular activating system maintains the State of wakefulness by high neuronal ng ene. The Idan s wells the pons and medulla aveive, CConsequetyring single genes wth mejor etn thesleep-wake eee and cing thas mode of acer mach more chalnging than in ster organisms ‘Theme 3: Simple Invertebrates Hold Out Promise for Studying Molecular Aspects of Sleep-Wake Rhythms Many radian uestions about sleep resin FROQLEMS it SLEEP RECLLATION STUDIES. The difice 'y of moving beyond intresting theories to papain 368 Chapter 11 genes involved in regulating any circadian process such Svsleep that sleeps very complea behavioral state “raitnal studies have vestigated sleepin mammals in birds. Episodes of skepin these species ze realy ‘eogelable because the llshare the mar carace ister of human sleep In reality, the Behavioral al mark of prolonged immobility reduced responsive ‘ess and Pomerat rebound fer depaation er not eset t binds and manna, but ane found In ‘umber of species voughout the animal Kingdon Ingovative research on cteadian mutant modee Is tleeadybelping speed up the rate of sucess sleep research, “Two phylogenetically simple animalsare possible ‘model forthe molecule genetic tof sep because ‘ten eltvly spl anual share a age number of {hair genes with humana, Including mapr classes of fenesinvoived in neural neon in hm dieses. Consequently widening the sopeof nina sleep mod ‘de could be uf steep: Resear an ne fature wil Imake more and more wie of animals in hich genetic rrscarch i reltively simple, productive, nd iexpen= ‘Sve (gure 117 Although a simpler mod syst so ‘ice the obvious relevance of studying mammals tliows for very important gains in effcency and com prchensvenes The point of studying simple arial Thatextbitea seepte state ito appre the question father conserved genetic mectanns ex frre ‘lating the stats of arousal. Broly corserved fun ‘ons fo the state may exist ADVANTAGES OF DROSOPHILA, Much of the sleep ‘escarch with elatively simple invertebrate species has Focused on the nematode worm Caco lees, And te frit hi, Drspllaelegater Historclly, fruit fes have provided an excelent syste fo unde Sanding genetic. Frat fies are effective models or $Mudying gene conrl of at only development and ‘metabolism, but als such complex behave pars a5 courtship leaming, and ceadtonehyths Tegeenre er FIGURETLZ Factor aleting he chee fs model tm for seep fesorch (Coursey or} Hes) rasp otas excellant genetic databases, to for rmaniputing genes, an the benefit inherent 9 any ‘mpl sytem. Automated metods for saying loc motor arabe well essblished and can ex be ood te to analyze the dats forrest and also for att. [Adule ies have aie span of several weeks, during ‘whlch they exhibit an aray of complex behavios pa teens mn contact, worms live for ony 9 few days nd reitively te cation information non about he twommof oie, ela Frit hes have a iredian cet pase with behay for le fstures that include a prefered posture and Joaation and an increased spore threshol. Prior 0 entering thei ceadian est phase, they adopt partic- tar poste, ace down onthe lor of the continer, Sind hen rain nat, eacpt for eptary move tment for periods up 25h during an average ttl Consolidate st prod of 7 oh rut Mesclsa show tence of oeding aloe. fes ae not allowed oes. ‘Tring the usual consolidated nightie ext period, they extbita subsequent rest ebound with incensed es during the ensuing ecovery pero. ‘Studies have been carried out with Drosophila on an important cellular signaling pathway Most eukaryotic cells contain signaling pathways that allow extracel changes oaffet gene expression nthe huceus Sich psthways allow cells hanger com leant of proteins and thereby allow animal adapt toenvionmentl changes ina common galing pat ‘ray binding of mall molecules to weeps onthe cll, ‘race results in intesed production ofa modified ‘eco called lic adenosine monophosphate eye [AMP or cAMP fr shot). Cele AMP in tum binds oa protein comple, resulting inthe release ofan active Finase, PRA, that moves tothe nucleus and phosphary- Inter poi call CREB. Tis phosphorylted CRE then has the ability fo activate gene expremion. The CAMT-PKA‘CRES pathoay teint fring acd for consoldation of lantern nels “Atv question was whee the proses ‘vasa important for eglting Spat fest Baa long ter memory consi tes apparently ostere by sleep xa mals cerning the cv of gene inthe Patoay might change deep and walking ‘arites of fies are tvallble with ‘mutations and wansgenes that change the fetivity of components ofthe pathway Experiments showed convincingly that tivity ofthe cAMP-PKA-CRES pat tray ss negatively corented with the cunt of Gly et Inte sx genotypes ctomined, the more cAMP att the rE | 2 aah [FIGURE 118 Relationship of cAMP acy rs nein ‘hrmuantortanapente enogpro i fee. When ‘Xpcie moun’ of AMPaciny aeeguune onan Se cman rtd by he oat ie ‘CAMP pathway, theless rest time the animals exper ‘ced (Figure 1.8). Blocking CREB stvty produced ‘imal that had gat difletyzecovering fom re ‘eprivation. These animals didnot return to normal ‘mounts of walang even 3 day fer est was dicup ‘aor ohe Because ofthe nature ofthis fatwa, his “lscovey should improve an understanding of which ‘CREB related genes foster wakefulness Modern tools ‘can help idently genes that are reputed by CREB, Micoatayscan be used to examine the genes whose ‘expression Is changed when CREB act altered Further comparative studies of such candies in fai fies and mammals could show how ths molecular pathray changes the ability of animals stay awake int ecover fam rest deprivation A second productive line of investigation focuses ‘on the role of Clock genes in regulating rest ‘Selective diruptios of dock fanetion in es have been ‘cried out as described in Caper? Bre the ck regulate et-acivity timing these eruptions should change the mango est ntact Suresing they Also changed the total ann of et nade Martone when mats ofall ofthe central clock genes were Studied, les with a nal mutation ofthe eve gene Showed a pronounced and unique phenolype of hangs in et regulation tht are diferent in males and Females Feral witha ull mutton sespoded fest deprivation with an enormously exaggerated rest ‘noun Some ofthese is ded when es deprivation ‘was prolongs. To test wheter theres depivation vat 2 genera senor the eet of oher tress manip tone was examined. The fies were not generally es Looking Forward 369 le bot instead seemed specifically susceptible to rest deprivation Clesly these mutants re abnormally erable to rest cepvatin, The mutans also alle increase expresion of froup af genes normaly induced by Ural sess those Ut encodeheat shock proteins These gens gen erally respond to sires, including rest deprvation ‘Thvough the use af rangene tht nceased fe expe: sion of specie heat shock prowin the abnormal est ‘ound ae theta eft fret depeivation cul be ‘ountraced inthe maton fis, Thus ¢ poise riches ‘een estab between est ee an ses lean, “The detain of speci candidate gene king rest deprivation to eal outcomes an inprkn i ing because can bese to deve gent selection foe ies hat encode the proteins involved in this rege tio. Futher tudes wil acs on understanding ow rt depevntion produces these changes, ae! the fener By of hs mechanism, vestigations of gence dle. ces ince mutans wl dan oon diension, Studies of gener dferencesin sep as at js sa Ing it mammals Ifa gender dimorphism s found in Feu Best may allow for rapid progress in under. standing the macular bass os iterence Tike CREB, CYCLE isa protein that regulates gene transcrip CYCLE sls in the Dspace tn feedback loop ith its partner CLOCK to make 4 Aimerie compe that activates expression of sever iene in theca cyl, ching er i an (Chapter 7; CHCLE-CLOCK the Dep counterpart Of the PAS-PAS heterodimeric transrpton actor fond noe eukaryote dock endack ops ima ‘malian counterparts BMALL The use of molecu ogi tol to deny wich cjlergulated genes ae "volved inthe rest phenotype shuld be iho Because both the cAMP-PKA-CREB pathway and 1 core creado odbc lop involving CYCLE se onsteved in mammal, new finsings soo re In Drosaphia should suggest rial approshes in mame ‘mals Tho umber of mutans ana rrapensc toe 3 Bio investigate genetic pathways generally grenter in flies than in mammals In adlton, studies in mar ‘alsa mich more tmeconsuming and experi. Fo these eons tis ener ty expeiments tate the cmologous genes and pathrysin fs before step {ng them in mammals. General regustory mechan seo conserve lang with he preci roles of genes ‘This wasthe cae with the ceeadan feedback lop Can single-gone mutants affecting see beldentined?™ wae Predicting the molecular mechanisms that mei Wak ingand le diticl Istats of consciousness were repulated lke ecadian rhythms, then » pareular 350 Chapter 11 molecular pata, o small group of interacting {eres might pce makes and seep. Cent) Saab ats makes at hypotenseoiyf ESCN of mammal asl clectonof sero ina Cicada ts ect aed cet oc ‘clan hyn comet acti but compare Step center as never ben found Most fhe am allan brain nrmallypatipatesin changes incon ‘Sous ltl inert mip os peo "Wires acs can vie otenaiy wel wie uta cratan Soak sep ay be ral frou sip ately val fanchn cmplt abolition fle tray otbe adobe blest Al ei tay ube dated by mulfpe edundan gees. As ‘re rekon se gene or gee pny tna nota ep Fly he pees at ened the CiCTE ant CREB pron andre own parte {heey areslacinvlved moter portant spect of {lft Manipulating the incon fsck eres Seay not ve apes lec on sep. Conaqsenly, ‘towing conchae about uti ay Be iia Although he answer kel tobe comples the seochshuld tsp Even elaborately tems meaning! igs on be gun rom sek the es of spc psthwnys Compurstons a {roms tole aval camino espe {Eger inva nba ptr sl he gun {loves of expan of ges ithe peoe da ing lfc Sehovioa sist Such © manned, Gueeiative apron wlbe rede dase he ie tie merece tena volved sleeps wel oon other cade behavioral processes. The eventual SShemate of he msec oy of ep may ote Since pathy Intend maybe a eto with Canc onder fe varus el igang snd mabe pathways bavig different bt pero overlapping ‘le The ae ay ao show tne and peop fey and pertups gender dimorphism Even deeap ‘etl and gig ferns nay be nor Incanto he ut fy model tats he power efcompurntvetilgy Prt satel ise ad Snospensive toe They aso provides boar py sentic boc frandestanding season presen ‘Theme 4: Another Breakthrough Discovery Is the Widespread Distribution ‘of Periphera Pacemakers!" (One ofthe first mammalian pacemakers to be discovered was the retinal clack of golden hamsters Foe many years fer the covery of the SCN in 1972 the ‘mammalian cradin system apposed ibe monic in having ony one chief central pacemae: The cent ‘ving self ofthe SCN ws ved asa ajr evo Tony change from the moltipieoelltor and mul. peptic input rangement sen inal oer erate froups Then meiuing nes dats in amals ggeted Utindependent oa eniitry soem ext oie {he SN 199 surprising new creadian raralan pacemaker was announced, edn alin the et, By culturing whole retina ina flow-through chamber, investigators could fellow the melatonin sates and secretion tytn fra long as day. The proper of {hisystem semble tho oe SEN ie Inretinas of wild-type haters the free-runcing period in constant darkness was closet 2 i ‘mutant hamsters, the period was shortened, having a ‘es simular fo those of fre-iving ita! mutants The retinal chythms could be phaseshifed by light and ‘ntaed to UD cycles. The fact thatthe ets pe ‘Shen lated retina ae could be phase shed 3s Wella entsine iictd that ot ight input an the ‘Sellar el were located in the eye ‘Bacauseo th ceri fel in mammalian wer, nolnforration i avilable for the heater eal lock ‘on localization of the cicadan functions in particular ‘ypesof retinal el Lit known othe call physiol {prof such peripheral ceilstrs, However vey recent fats sige tthe clocks ot merely» pep fra lal pacemaker within the eye, but ha i ctaly trteracs it the SCN to regulate ie ythmi utp Thi ist indication ofertas SCN autonomous olor: sn manmals foreshadowed the meogtion of many the independent or at least al sal sustaning calls. One recent promising development in circadian ‘research has been the application of transgenic {echnology to cell culture of sect and ‘mammalian pacemaker tissves*=™™0 OVERVIEW. Transgenic marker techniques had previ fusly been used succesfully for the unicellular ‘janobocterium Syecous and for Ue stars plant ‘Arado The adapain ofthe general reporter el nique proved more dificult for advanced invertebrates 1nd veribrate species. Then in 1997, the development If eporter syste in Dope pve new mpe 2 ‘hestay of peripheral osclators 9 athopos invert brates ad annals sr abo Chaps, and) The bolumineacent Luciferase gene a was fase fo the por fg2ne of Drosphin o forma or-tuc construct. By th ‘ans a fythmic visible reporter system was made Satlnble that could easily be racked over considerable erode me fy scl TANSCENE TECHNO. The gest advan tage ofthe perc construc that it san exelent ore stdin! marker for allowing the phased pena ‘eeadian hythens with minieal disturbance tothe fngenism,Bioluminescent light emission i recorded photographically. ‘Artltemativ method ie the us of priven geen Aorecent protein as the epoter, Usiag Desi s ‘ists examined jer eslatons in who iets an in ‘ultured body segments, nlsding head, thoray and Siadomen.Rhyshmiety Was exprened in DD and LD by {he iat fu fy The sures fac, however that all hve segments in colture sso showed robust ard Wwidesprend yt nD the eye fe on but With felatvely Low amplitude In LD the rhythos ental to shifted light cyl Other bay pats such fs prooscss and antennae were le oselatery in LD Sd DD (igure 113). The expresrion was found st ea. Uy single-cell evel n lege ae wings, Furthermore s- nits made the major Secvery tat every oslltory {sue in Draco photreceptive ‘Why had’ the phenomenon of self ustaned oxi Isto activity in mulpte pat the body ben noted previously for more animals? Probably tne reason Involved the method of recording ryt. The in til evidence for central pacemakers had come primar 'y from behavioral data of inact organisms Lovomotor ‘tivity of individual ls and eclosion yt pop lations were the prefered overt shytnme measured (Oly win transgene reporter methods were sed did the tissue an elev! eythans Become apparent in Dros REVEALED fY TRARSCENIC MARKERS. The prevaling en foc sevetl decades in chuonabology rsh had been ‘hat multiple oseilstors were prevalent only in non ‘mammalian groups. The overlapping ols of pins land retinal pacemaker and SCN pacemaker ofp Us and bees were well-known exaples- An ine break in that unified facade wa the demonstration of fan autonomous ctcadian clock in hamster retina Seseribed inthe previous scion, [Atabout this time, one group of scent made an !emportant discovery, Fibvoblsts that had Bee in cu ture for a quater ofa century could be induce fo become yhmic agin. The ifeiction of ts phe- nomenon was possible because clock genes and pro teins inthis case Pet and Per, were kaon, and tet ‘expression could be followed without deed! under Sanding of the tythac biology of thee ell Ons “portant extrapolation was vio I bbls have clock why not iver cl hese cel, al flies oF ter cls that cannot peresive igh? ‘Soon another piece of evidence fr independent peripheral oscillators ome ram eh transi a looking forward 371 : és g FIGURE 119 fre running ceadian bioluminescence ‘tins ee ow fr teeco Briann cabure Con Gye Saad 705 (dys tom Peet a, 9) “Much asin the case frp-tue Drei, the tansgeic rats express the Pr gene activity vy by mean 9 Bioluminescent lcierin mathe fap linked tothe Per ‘gene. When SCN ts wae expand from a Pele Tranageni at and maintained in constant conditions © ‘oraian rhythm witha nee 24h period persisted for $2days invite. Even more surprising the persistence ‘of shythmicity in cultured pieces of ve, lg. and ‘elotal muscle taken fom the anogenic rats gure m0, Frther discoveries soon mteriaied, Peripheral locks appeared egulted loosely by the SCN but ee fntrained independent afer abrupt phase shifts of the ligh schedule. Using the tanagenic rat model researcher studied effects of competitive light cycles fan food svalbilty a5 entaining agents iat ats 37 Chapter tt isi . came samo} ste pew ee AL FIGURE D140 Riythy of cultured tage ver tels:Bokuminen reper ores wa a tw ‘ian actif) Cane mop. fy kl (8) SCN NDB fora dys (€) Coparaeno pret sy ue peat Rh ang rom ae Theiver locks could beets by reste feng sched, much a inet ats ein fo esti font ing schedules Food entrainment occurred even when a light eee was provide that was ut of phase wath the feeding schedule. Altbough SCN shyt maid linked to the LD regime, the ver was apy eitelne by restricted feeding Shs ay ge a 10h wee secon plished in2 days These ess challenge the wees. lished concept ofa mammalian circadian hierarchy dominated bythe SCN ar central pacemaker Infact, many types of els do Mave clocks The od ‘cw ofa dominant clockin one es ike the SEN hae [em way toa new view af clockshop of highly ters ovected osclstors The biology of most of eee os Inspect of nmap Sl iestha they cartel ae stillargey unknown: cen year this shin thinking has Fesulted In name ‘hage frm crc clack to cretion pagan The ‘err denotes the dstinion been single paces dtating dine forthe organism and group ofits Coupled clocks collectively providing an inteal mes re fie coretycoornated th den and dusk Though seasonal changes in day length, The program Isadck shop of couple oellafry some sles ing nd some damped. Theme 5: Single Independently Oscillating SCN Clock Cells Are Coordinated into a Muiticellular Regulator of Behavioral Output Rhythms?» Chimera technology is providing answers about ‘the contrl of circadian behavior by the ensemble ‘of osifators in the SCN” BACKGROUND. Recently singe pacemaker cells have been shown fo osillat independently in culture, wih 8 cel-specii free-running period (ace Chapter 6, Obvously the differing periods of many clock ells rus: somehow be modulated fo yield an integrated ‘output command tthe higher organizations ievels and eventually f9 behavioral output One approach to “undrstanding the iterations of empty of SN ‘oscilatrs has been the chimera paradigm i this demanding technology. chimeric mice sre produce wid have varying proportions of mutant SCN cell and wild-type SCN callin the experiments described inthe next ection, the differing proportions of cella seroma series of chimeric indvidunts pve clus tthe proces of czcaian regulation of behovior in 2002, Sharon Low-Zeddies war a co-eipiont ofthe Donal B Lindsey Prize in Behavioral Neurecience fom the othe ear in recognition of thiselepan ted. METHODS, The dais simple the procedures ar ery complex in 1843 semicomioat mutation a lack ‘was iced in ie that resuled m prominent mf ‘ation ofthe ceadian prod and ampitea he ingens activity shyt, as well as phase siting by ight The wily period was about 237, witha robust creaian hth and » normal phase response Curve Heterozygous mize dif by showing lengthened looking forward 373 FIGURE DAI Astdy of mm SinBne ented in ek ahr @ @ erpise recto Cink chimeric spews Dati Spe tp sn ween Ete eect caret el aos ton pot oo amp It rch ct whch ine hat ita sain hs cea (C) Double piloted sctvity we sei Seer ‘BD period between light pulses decreased ample of tytn and a heightened response hase shiing by ight signal, Homozygous mice were usally inal weakly hyn ih ggecatd legen ot pes td Betveen 27 and 28 under constant conor, bot they ‘lek Decme seni ee Figure 11198) The period has now been sown oes nse scilating pacemaker cel em wild-type aed Clack mutant ice Under invita cule cngisons “These features were stlzed in the chimera experiment. “wostane of me wee fst fererated to provide suitable embry for ceting the civadian pel for unnng-wheel att. The other shimeras (Figure 1.11Aand B, One was awildsype Stain wasan abbng homage nator ones, srsinwihcntcolo asa overt mathr ancl aLacZeel_ahythnccicadan perad ot kabel elect a smaskerfor he SCN cel Ths stain eibted anormal et. Pals of wildtyre mad must eiteer ne oe = Aad LLDDAAFA LAE HULL ELLE LA, ang a is i444, 444 da aA Bu HAE, cea oN ae athe os Bs AAA 2d 44 ES Woe ee S58: “¢ FIGURE 142 Wheel running econ for 17 Chek sown espe fom rep sel moron let mae a a embryos were aggre in vito to frm chimeric bs tocysts The compeste embryos were then transferred int surrogate thers 6 continue development Random inerminglg ow type ee mutate takes place within a chimes embryo during develop ‘ment such that exc chimers individ coisa gue

    You might also like