CircadianandVisual Neuroscience
Editedby NayantaraSanthi
DepartmentofPsychology, NorthumbriaUniversity, NewcastleUponTyne,UnitedKingdom
ManuelSpitschan
TranslationalSensory&CircadianNeuroscience,MaxPlanck
InstituteforBiologicalCybernetics,Tubingen,Germany
Chronobiology&Health,TUMDepartmentofSport andHealthSciences(TUMSG), TechnicalUniversityofMunich,Munich; TUMInstituteforAdvancedStudy(TUM-IAS), TechnicalUniversityofMunich,Garching,Germany
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Contributors
AnnetteE.Allen
CentreforBiologicalTiming,DivisionofNeuroscienceandExperimentalBiology, FacultyofBiology,MedicineandHealth,UniversityofManchester,Manchester, UnitedKingdom
BeatrizBan ˜ o-Ota ´ lora
CentreforBiologicalTiming,DivisionofNeuroscienceandExperimentalBiology, FacultyofBiology,MedicineandHealth,UniversityofManchester,Manchester, UnitedKingdom
JohnL.Barbur
CentreforAppliedVisionResearch,TheHenryWellcomeLaboratoriesforVision Science,SchoolofHealthSciences,City,UniversityofLondon,London, UnitedKingdom
PabloA.Barrionuevo
InstitutodeInvestigacio ´ nenLuz,AmbienteyVisio ´ n,ConsejoNacionalde InvestigacionesCientı´ficasyTecnicas—UniversidadNacionaldeTucuma ´ n, Tucuma ´ n,Argentina
PeterBlattner
FederalInstituteofMetrologyMETAS,Bern-Wabern,Switzerland;Presidentof theInternationalCommissiononIllumination(CIE),Vienna,Austria
DavidH.Brainard
DepartmentofPsychology,UniversityofPennsylvania,Philadelphia,PA, UnitedStates
TimothyM.Brown
CentreforBiologicalTiming,FacultyofBiologyMedicineandHealth,Universityof Manchester,Manchester,UnitedKingdom
HugoCalligaro
SalkInstituteforBiologicalStudies,LaLolla,CA,UnitedStates
AshleyE.Copenhaver
DepartmentofBiologicalSciences,UniversityofMaryland,BaltimoreCounty (UMBC),Baltimore,MD,UnitedStates
NicolasP.Cottaris
DepartmentofPsychology,UniversityofPennsylvania,Philadelphia,PA, UnitedStates
OuriaDkhissi-Benyahya
UnivLyon,UniversiteClaudeBernardLyon1,Inserm,StemCellandBrain ResearchInstitute,Bron,France
GregJ.Elder
NorthumbriaSleepResearch,DepartmentofPsychology,FacultyofHealthand LifeSciences,NorthumbriaUniversity,NewcastleuponTyne,UnitedKingdom
RheaT.Eskew,Jr.
DepartmentofPsychology,NortheasternUniversity,Boston,MA,UnitedStates
DorotheeFischer
DepartmentofSleepandHumanFactorsResearch,InstituteforAerospace Medicine,GermanAerospaceCenter,Cologne,Germany
ElisabethFlo-Groeneboom
DepartmentofClinicalPsychology,FacultyofPsychology,UniversityofBergen, Bergen,Norway
RussellG.Foster
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,NuffieldDepartmentofClinicalNeurosciences, UniversityofOxford,Oxford,UnitedKingdom
JingyiHe
DepartmentofPsychology,NortheasternUniversity,Boston,MA,UnitedStates
CassieJ.Hilditch
FatigueCountermeasuresLaboratory,DepartmentofPsychology,SanJoseState University,SanJose,CA,UnitedStates
AnyaHurlbert
CentreforTransformativeNeuroscienceandInstituteofBiosciences,Newcastle University,NewcastleuponTyne,UnitedKingdom
LuisA.Issolio
InstitutodeInvestigacio ´ nenLuz,AmbienteyVisio ´ n,ConsejoNacionalde InvestigacionesCientı´ficasyTecnicas—UniversidadNacionaldeTucuma ´ n; DepartamentodeLuminotecnia,LuzyVisio ´ n,FacultaddeCienciasExactasy Tecnologı´a,UniversidadNacionaldeTucuma ´ n,Tucuma ´ n,Argentina
AntoninJandot
UnivLyon,UniversiteClaudeBernardLyon1,Inserm,StemCellandBrain ResearchInstitute,Bron,France
TaraA.LeGates
DepartmentofBiologicalSciences,UniversityofMaryland,BaltimoreCounty (UMBC);DepartmentofPhysiology,UniversityofMarylandSchoolofMedicine, Baltimore,MD,UnitedStates
RenskeLok
DepartmentofPsychiatryandBehavioralSciences,StanfordUniversity,Stanford, CA,UnitedStates
TakumaMorimoto
DepartmentofExperimentalPsychology,UniversityofOxford,Oxford, UnitedKingdom;DepartmentofGeneralPsychology,Justus-Liebig-Universit€ at Gießen,Gießen,Germany
JoshuaW.Mouland
CentreforBiologicalTiming,FacultyofBiologyMedicineandHealth,Universityof Manchester,Manchester,UnitedKingdom
RubenPastilha
CentreforTransformativeNeuroscienceandInstituteofBiosciences,Newcastle University,NewcastleuponTyne,UnitedKingdom
StuartN.Peirson
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,NuffieldDepartmentofClinicalNeurosciences, UniversityofOxford,Oxford,UnitedKingdom
CarinaA.Pothecary
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,NuffieldDepartmentofClinicalNeurosciences, UniversityofOxford,Oxford,UnitedKingdom
OscarU.Preciado
InstitutodeInvestigacio ´ nenLuz,AmbienteyVisio ´ n,ConsejoNacionalde InvestigacionesCientı´ficasyTecnicas—UniversidadNacionaldeTucuma ´ n; DepartamentodeLuminotecnia,LuzyVisio ´ n,FacultaddeCienciasExactasy Tecnologı´a,UniversidadNacionaldeTucuma ´ n,Tucuma ´ n,Argentina
LukeL.A.Price
CentreforRadiation,ChemicalandEnvironmentalHazards,PublicHealth England,Chilton,HarwellCampus,Didcot,Oxfordshire,UnitedKingdom; SecretaryofDivision6forPhotobiologyandPhotochemistryofCIE,Vienna, Austria
RoshaeC.Roberts
DepartmentofBiologicalSciences,UniversityofMaryland,BaltimoreCounty (UMBC),Baltimore,MD,UnitedStates
Marı´aL.SandovalSalinas
InstitutodeInvestigacio ´ nenLuz,AmbienteyVisio ´ n,ConsejoNacionalde InvestigacionesCientı´ficasyTecnicas—UniversidadNacionaldeTucuma ´ n; InstitutodeInvestigacionesenBiodiversidadArgentina,FacultaddeCiencias NaturaleseInstitutoMiguelLillo,UniversidadNacionaldeTucuma ´ n,Tucuma ´ n, Argentina
Ma’ayanSemo
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,NuffieldDepartmentofClinicalNeurosciences, UniversityofOxford,Oxford,UnitedKingdom
KeizoShinomori
SchoolofInformation/ResearchInstitute,KochiUniversityofTechnology,Kochi, Japan
MelissaA.St.Hilaire
DivisionofSleepandCircadianDisorders,BrighamandWomen’sHospital; DivisionofSleepMedicine,HarvardMedicalSchool,Boston,MA,UnitedStates
LauraC.E.Steel
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,NuffieldDepartmentofClinicalNeurosciences, UniversityofOxford,Oxford,UnitedKingdom
S.K.E.Tam
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,NuffieldDepartmentofClinicalNeurosciences, UniversityofOxford,Oxford,UnitedKingdom
YeseniaTaveras-Cruz
DepartmentofPsychology,NortheasternUniversity,Boston,MA,UnitedStates
SelmaTir
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,NuffieldDepartmentofClinicalNeurosciences, UniversityofOxford,Oxford,UnitedKingdom
VladyslavV.Vyazovskiy
SirJulesThornSleepandCircadianNeuroscienceInstitute(SCNi),KavliInstitute forNanoScienceDiscovery,DepartmentofPhysiology,AnatomyandGenetics, UniversityofOxford,Oxford,UnitedKingdom
BrianA.Wandell
PsychologyDepartmentandtheStanfordCenterforImageSystemsEngineering, StanfordUniversity,Stanford,CA,UnitedStates
JohnS.Werner
DepartmentofOphthalmology&VisionScience,UniversityofCaliforniaDavis, Sacramento,CA,UnitedStates
JamieM.Zeitzer
DepartmentofPsychiatryandBehavioralSciences,StanfordUniversity,Stanford; MentalIllnessResearchEducationandClinicalCenter,VAPaloAltoHealthCare System,PaloAlto,CA,UnitedStates
1. Thebasisofphysicalphotometry..................................................2
1.1AdditionalnotestoEqs.(1)to(7)..........................................4
2. Colorimetry....................................................................................4
3. IILresponses..................................................................................7
3.1AdditionalnotestoEqs.(14)and(15)...................................9 4. Conclusions....................................................................................9
1. Introduction..................................................................................14
1.1Thesilentsubstitutionmethod..............................................14
2. Opticalstimulationsystems.........................................................15
2.1Nonimage-formingarrangements .........................................15
2.2Image-formingarrangements................................................19
3. Characterizationandcalibrationprinciples.................................25
3.1Stimulatorresponsecurve.....................................................26
3.2Spectralpowerdistribution...................................................28
3.3Additivity..............................................................................30
3.4Modulationtransferfunction ................................................30
3.5Spatialuniformity.. ..........................30
3.6Temporalstability.................................................................31
3.7Sourcesofartifacts................................................................31 4. Conclusions..................................................................................32
CHAPTER6Rodentmodelsintranslationalcircadian photobiology ............................................................... 97 SelmaTir,LauraC.E.Steel,S.K.E.Tam,Ma’ayanSemo, CarinaA.Pothecary,VladyslavV.Vyazovskiy, RussellG.Foster,andStuartN.Peirson
1. Introduction..................................................................................98
2. Theroleofrodentmodelsincircadian photobiology.................99
3. Translationalcircadianphotobiology.... ....................................100
4. Strengthsandlimitationsofrodentmodels...............................101
4.1Strengths..............................................................................102
4.2Limitations..........................................................................103
5. Futuredirections........................................................................105
6. Conclusions................................................................................108 Acknowledgments...........................................................................108 References.......................................................................................109
CHAPTER7Slowvision:Measuringmelanopsin-mediated lighteffectsinanimalmodels ................................. 117
AnnetteE.AllenandBeatrizBan ˜ o-Ota ´ lora
1. Introduction................................................................................117
2. Methodsofstudyingmelanopsinatasystemslevel.................122
2.1Eliminatingrod/coneresponses..........................................122
2.2Manipulatingmelanopsinactivity......................................123
2.3ModulatingipRGCactivity................................................124
2.4Stimulusspectraandreceptorsilentsubstitution...............124
3. Melanopsincontributiontononimage-formingfunction: Methodsandfindings.................................................................126
3.1Circadianphotoentrainment................................................126
3.2Pupillarylightreflex...........................................................130
3.3Sleepandbehavioralregulation.........................................131
3.4Moodregulation..................................................................132
4. Closingremarks.........................................................................133 Acknowledgments...........................................................................135 References.......................................................................................135
CHAPTER8Beyondirradiance:Visualsignalsinfluencing mammaliancircadianfunction ............... ................. 145
JoshuaW.MoulandandTimothyM.Brown
1. Introduction................................................................................145
2. Experimentalparadigmsprovidinginsightintothe photoentrainmentmechanism....................................................146
3. Evidenceforinnerandouterretinalsourcesofcircadian control........................................................................................149
4. Retinalphotoreceptorspecializations........................................151
5. Rodcontributionstocircadianphotoentrainment.... .................153
6. Conecontributionstocircadianphotoentrainment..... ..............155
7. Spatiotemporalpropertiesofcircadianresponses.....................158
8. Doinsightsintorodentphotoentrainmenttranslateto humans?......................................................................................160
9. Conclusion..................................................................................161 References.......................................................................................163
CHAPTER9Circadianphotoreception:Theimpactoflight onhumancircadianrhythms ................................... 171 JamieM.ZeitzerandRenskeLok
1. Phaseresponsecurve.................................................................172
2. Durationsensitivity....................................................................174
3. Intensityresponsecurve.............................................................175
4. Spectralsensitivity.....................................................................176 References.......................................................................................177
CHAPTER10Modeling(circadian)
1. Introduction................................................................................181
2. Foundationalaspectsofmodelingthecircadiansystem...........182
2.1ProcessC:Asimplesinusoid.............................................182
2.2Oscillatormodelsofthemammaliancircadiansystem.....183
3. Representationoflightinmodelsofthecircadiansystem.......185
3.1Power-lawrelationshipforcircadianlighteffects...... .......185
3.2ProcessL:Thelightpreprocessor....... ...............................186
3.3Beyondluxaslightinputtomathematicalmodels ofthecircadiansystem......................... ..............................187
3.4Temporaldynamicsoflightandcross-species comparisons.........................................................................189
4. Applicationofmathematicalmodelstoimprovehuman healthandperformance..............................................................191
4.1Predictionsofneurobehavioralperformanceand alertness...............................................................................191
4.2Individualizedpredictionsofcircadianphase....................192
4.3Generatingtestablehypothesesforlighttreatment andfutureexperiments........................................................193
5. Conclusions................................................................................194 References.......................................................................................195
CHAPTER11Visualencoding:Principlesandsoftware ..... ......... 199
BrianA.Wandell,DavidH.Brainard,and NicolasP.Cottaris
1. Introduction................................................................................199
2. Representingthesceneradiance................................................200
2.1Planarscenes:Calibrateddisplay.......................................201
2.2Planarscenes:Naturalimageapproximation.... .................202
2.3Displayvariation.................................................................204
2.4Three-dimensionalscenes...................................................206
3. Optics:Theretinalirradiance....................................................208
3.1Imageformation:2D...........................................................209
3.2Imageformation:3D...........................................................213
4. Lighttransduction......................................................................215
4.1Rodandconephotoreceptors..............................................215
4.2Intrinsicallyphotosensitiveretinalganglioncells..............224
5. Examplecalculations.................................................................226
6. Summary....................................................................................226
References.......................................................................................227
CHAPTER12Visualpsychophysics:Luminanceandcolor .......... 231 YeseniaTaveras-Cruz,JingyiHe,andRheaT.Eskew,Jr.
1. Introduction................................................................................231
2. Psychophysicalmethods............................................................233
2.1Classicalmethods................................................................235
2.2Signaldetectiontheory.. .......................237
2.3Adaptivemethods...............................................................238
3. Selectedresults...........................................................................239
3.1Luminousefficiencyandspectralsensitivity.... .................239
3.2Colorvision.........................................................................242
3.3Spatialandtemporalsensitivity:Effectsoflightlevel......247
4. Finalthoughts&resources........................................................253
4.1Additionalresources...........................................................253 Acknowledgments...........................................................................254
References.......................................................................................254
CHAPTER13Agingofvisualmechanisms .................................... 257 KeizoShinomori,JohnL.Barbur,andJohnS.Werner
1. Introduction................................................................................257
2. Opticalchangesassociatedwithaging...... ...............258
2.1Senescentchangesintheeyepupil ....................................258
2.2Senescentchangesinpreretinalfilters...............................259
2.3Senescentchangesinretinalimagequality........................261
3. Senescentchangesinsensitivityofrodandconepathways.....262
3.1Darkadaptationandrodsensitivity....................................262
3.2Age-relatedchangesinconesensitivity.............................263
3.3Colordiscrimination...........................................................263
3.4Spatialvision.......................................................................265
3.5EstimatingsensitivitychangesofipRGCs.........................266
3.6Temporalvision..................................................................268
4. Anoteaboutunconsciousvisualprocesses...............................270 References.......................................................................................271
CHAPTER14Seeingandsensingtemporalvariationsin
1. Measurementsofnaturalilluminationovertime.... ..................277
1.1Thechromaticitiesofdaylight............................................277
1.2Temporalvariationsindaylightchromaticityand illuminancefromdawntodusk. .................280
2. Thedualhumanresponsetolight.............................................287
2.1Responsestolightinnonvisualpathways..........................287
2.2TheroleofSconepathways..............................................290
3. Measuringperceptionoftemporalvariationsinillumination...292
3.1Visualdiscriminationoftemporalchangesin illuminationchromaticity....................................................292
3.2Perceptualthresholdscomparedwithnatural illuminationtemporalchangecharacteristics.... .................295
3.3Nonvisualandvisualmechanismsunderlyingthe discriminationoftemporalchangesinillumination...........296
3.4Implicationsandopenquestions.........................................297 Acknowledgments...........................................................................297 References.......................................................................................298
CHAPTER15Lightinecologicalsettings:Entrainment,
1. Introduction................................................................................303
2. Entrainmentinhumans:Lightasthedominant zeitgeber ........305
2.1Modelsofentrainment........................................................305
2.2Chronotypes.......... ............308
3. Circadiandisruption:Howmisalignedlight-darkcycles candisruptthecircadiansystem................................................309
3.1Sleepregularity...................................................................311
3.2Positionwithinatimezone................................................313
3.3Daylightsavingtime...........................................................313
3.4Shiftwork............................................................................314
4. Fieldstudies:Usinglighttomitigateeffectsofcircadian disruptioninecologicalsettings................................................314
4.1Phaseshiftingeffectsoflight.............................................315
4.2Zeitgeberstrengtheningandacutealertingproperties oflight.................................................................................317
4.3Non-24-hlight-darkcycles.... ............................318
4.4Challengesandrecommendations......................................319
5. Conclusion..................................................................................322 References.......................................................................................322 CHAPTER16Howcanlightbeusedtooptimizesleepand
GregJ.ElderandElisabethFlo-Groeneboom
1. Introduction................................................................................331
2. Normalage-relatedchangestosleepandcircadian rhythmicity.................................................................................333
2.1Sleep....................................................................................333
2.2Circadianrhythmicity.... ............................336
3. Canlightimprovesleepinolderadults?...................................337
3.1Brightlighttreatment..........................................................338
3.2Howmightlightimprovecircadianrhythmicity?...... ........339
3.3Howmightlightimprovesleep?........................................339
4. Methodologicalconsiderationsfortheuseoflightinsleep andhealth...................................................................................340
4.1Whatisthemosteffectivemodeofdelivery?...................340
4.2Whatisthemostfeasiblemodeofdelivery?.....................341
4.3Whatistheoptimaldose?..................................................342
5. Canlightbeusedtotreatclinicalproblems?............................344
5.1Physicalhealth....................................................................344
5.2Sleepproblems....................................................................344
5.3Moodanddepression..........................................................346
5.4Circadianrhythmdisorders.................................................346
5.5Prevention...........................................................................347
6. Conclusion..................................................................................347
Acknowledgments...........................................................................348 References.......................................................................................348
Foreword
Onewhokindlesthelightofawarenesswithingetstruelight.
—RigVeda,circa1500–1000BCE
AndGodsaid,Lettherebelight:andtherewaslight.
—Genesis,circa550BCE
Allthefiftyyearsofconsciousbroodinghavebroughtmenoclosertoanswerthe question,’Whatarelightquanta?’Ofcourse,todayeveryrascalthinksheknows theanswer,butheisdeludinghimself.
—AlbertEinstein,1951CE
Lightismiraculous.Lightsustainsourfoodchain,illuminatesourworld,andquietly controlsthechemicaltidesinourbodies.Humansarepredominantlyavisualspecies;ourmoment-to-momentwakingconsciousnessisfilledwiththesenseofvision. Ithasbeenestimatedthatmorethanhalfofthecentralnervoussystemisinvolvedin theprimaryandsecondaryprocessingofvisionandvisualreflexes.Itisnowonder, then,thatexploringthenatureoflightandcolorhasbeenapassionforprophets,mystics,philosophers,andscientistsacrossthemillennia.Brilliantminds,fromPlatoto GoetheandfromNewtontoEinstein,havepuzzledoverthemysteryoflightandits interactionwiththehumaneye(Zajonc,1993).
Thecentralthreadofthisbookistheinteractionoflightandtheeye.Itsynthesizeslightbothasastimulusforthesensorycapacityofvisionandfortheregulation ofcircadian,neuroendocrine,andneurobehavioralphysiology.Dr.Spitschanand Dr.Santhiaretobecongratulatedforfosteringthediversevoicesresponsiblefor thecollectedchapterscomprisingthisvolume.Importantly,theyopenedthedoor tomanyinvestigatorsintheearlierstagesoftheircareersforcontributingmostof themanuscripts.Thefutureofanyfieldofempiricalresearchalwaysdepends onanemergingcadreofinvestigatorswhobringfreshquestions,innovative approaches,andnovelinsights.Tobringbalanceanddiversityofperspectives, Dr.SanthiandDr.Spitschanhavejudiciouslyincludedcontributionsfromsome moreseniorinvestigators.Astonishingly,thisfieldoflightresearchisfoundedon frogsandswimmingghosts.
Morethanacenturyago,studiesontheNorthernleopardfrog, Ranapipiens, ultimatelyledtotheisolationandchemicalcharacterizationofthepinealhormone, melatonin.In1915,CareyMcCord,MD,andhisassistantFloydAllenconducted groundbreakingexperimentsfeeding R.pipiens tadpoleswithvariousbovinetissues. Totheirsurprise,tadpolesfedwithamixtureoffreshplantfoodanddesiccated pinealtissuelosttheirdarkpigmentation.Inaninterview,McCordrecountedhow
Allenexcitedlyreported:“Theylookedlikeghostsswimmingaroundinthewater withveryblackeyes!”Workingfromthisstunningobservation,McCordandAllen conductedcontrolledstudieson12,000tadpoles,therebyestablishingtheinfluence ofthepinealglandtissueonfrogpigmentation(McCordandAllen,1917).Progress haltedabruptlywhenMcCordjoinedtheNationalGuardtoserveinacoordinated missionbetweentheUnitedStatesandMexicotostopthenotoriousrebelPancho Villa.Aftercompletinghismilitaryservice,McCordreturnedtohaveaprominent careerinindustrialmedicine.
Afterretirement,McCordhadachanceencounterwithdermatologistAaron Lerner,MD,PhD,attheUniversityofMichiganin1952.Theyhappenedtosittogetherforlunchintheschoolcafeteria.McCordcaptivatedLerner’sattentionwhen theirdiscussionturnedtoMcCord’searlierfrogskinstudies.Thetwoscientistsmet severaltimestodiscussthepossibilityofisolatingtheactiveskin-lighteningagent fromthepinealgland.LernerlatermovedtoYaleUniversitywhereheandhis colleaguesembarkedonthatveryproject.
Overa4-yearperiod,Lerner’steamfractionedandtestedmorethan250,000cow pinealglandsinan invitro assaysystemof R.pipiens frogskincells.After3years, theyhitasignificantroadblock.Theteamwasinupheavalastheyrealizedthey wouldneedamillionmoreglandstoisolateapurehormonefromthepinealgland. Discouraged,theygavetheprojectonemoremonthtoprovideagoodleadbefore ceasingtheworkentirely.Oneweekbeforeshuttingdowntheproject,Lernerhad anintuitiveflashabouttheexactstructureofthepinealhormone.Hisinsightled themtoisolateaminisculebatchofmelatonin—aninvisiblelayerinthebottom ofanotherwiseemptyflask.Intheirfrogskinassay,however,itwas100,000times morepotentthanotherknownskin-lighteningagentssuchasnoradrenalineandacetylcholine.Thiscrowningachievementbroughtthearduous,4-yearprojecttoasuccessfulconclusion(Lerneretal.,1958).
Decadeslater,thediscoveryofmelanopsinwasalsopredicatedonresultsfrom studiesonthefrogskin.MarkRollag,PhD,andhiscolleagueschosetoworkwitha bioassaydevelopedfromthefrog Xenopuslaevis,commonlynamedtheAfrican clawedfrog.Rollag’steamwasinterestedinidentifyingthemelatoninreceptor andmelatonin’scapacitytoregulatecellphysiology(Whiteetal.,1987).Thosestudiesemployedan invitroXenopus melanophoreassay.Achanceobservationnoted thatthisassayrespondedtoverysubtledifferencesoflightandshadowontheir labbench,thushighlightingitsutilityinthestudyofextra-retinalphotoreception. In1996,IgnacioProvencio,PhD,ascientistwithabackgroundincircadianphotoreception,joinedDrs.RollagandGuisenJiangasapostdoctoralfellow.Theysetout toidentifytheactivephotopigmentinfrogskinmelanophores.Thisquestwas facilitatedbyemployinga Xenopus melanophorecDNAlibraryscreen,which provedinvaluablefornarrowingthesearchfortheactivephotopigmentintadpole skincells.After2yearsofintensivework,theprojectsuccessfullyculminatedin theidentificationandmolecularcharacterizationofthephotopigmentmelanopsin. InacollaborationwithWilliamParHayes,PhD,theteamdemonstratedthrough insitu hybridizationthatmelanopsinwaslocalizedinfrogskinmelanophorecells
aswellasinthefrogretina,iris,andhypothalamicnuclei.Thoseresultssuggested thatmelanopsinplayedaroleincircadianphysiologyaswellasinthephoticcontrol offrogskinpigmentation(Provencioetal.,1998).
Ultimately,photosensitivefrogskinwaspivotalinthediscoveryoftwokey molecules,thehormonemelatoninandthephotopigmentmelanopsin.Eachofthese moleculesiscitednumeroustimesacrossthechaptersinthisvolume.
Dr.SanthiandDr.Spitschanhavecuratedacollectionofcontributionswoven frombothfreshandfamiliarvoices.Thisbookisaninvaluabletoolforunderstanding ourpresentviewofhowlightstimulatestheretinatosupportvisionandphysiologicalregulation.Itisalsoaportaltothefutureofthisrapidlydevelopingfield.
GeorgeC.Brainard,PhD ProfessorofNeurology Director,LightResearchProgram ThomasJeffersonUniversity
Philadelphia,Pennsylvania
References
Lerner,A.B.,Case,J.D.,Takahashi,Y.,Lee,Y.,Mori,W.,1958.Isolationofmelatonin,the pinealglandfactorthatlightensmelanocytes.J.Am.Chem.Soc.80,2587. McCord,C.P.,Allen,F.B.,1917.Evidenceassociatingpinealglandfunctionwithalterations inpigmentation.J.Exp.Zool.23,207–224.
Provencio,I.,Jiang,G.,DeGrip,W.J.,Hayes,W.P.,Rollag,M.D.,1998.Melanopsin:anopsin inmelanophores,brain,andeye.PNAS95,340–345.
White,B.H.,Sekura,R.D.,Rollag,M.D.,1987.Pertussistoxinblocksmelatonin-inducedpigmentaggregationinXenopusdermalmelanophores.J.Comp.Physiol.B157,153–159. Zajonc,A.,1993.CatchingtheLight:TheEntwinedHistoryofLightandMind.Oxford UniversityPress,NewYork.
