2011.10.07.. TÁMOP–4.1.2-08/2/A/KMR-2009-0006 1 Peter PazmanyCatholicUniversity Facultyof InformationTechnology ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMS LECTURE2 HISTORY OF ELECTROPHYSIOLOGY www.itk.ppke.hu (Az ideg-és izom-rendszer elektrofiziológiaivizsgálómódszerei) (Az elektrofiziológiatörténete) RICHÁRD FIÁTH and GYÖRGY KARMOS ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 AIMS: InthislecturethestudentwillbefamiliarwiththehistoryoftheelectrophysiologythroughtheworkofmanygreatscientistsfromtheancienttimestotheXXthcentury. Physiology: The science of the function of the living systems. Electrophysiology: The branch of physiology, where the electrical activity of organisms is studied. Theword"physiology"wasusedfirstinwrittentextbyJeanFernelFrenchdoctor(1497-1558)inhisbook"MedicinaUniversa"(1552).Heusedthetermtodescribethestudyofthebody’sfunction. TheodorZwinger(1533-1588):"Physiologiamedica"(1610)isthefirstbook,whichcontainsthiswordinthetitleaswell. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 ANCIENT TIMES ThefirstwrittendocumentonbioelectricphenomenonisanEgyptianHieroglyph(B.C.4000).Itdescribestheelectricsheatfishorcatfishasafishthat„releasestroops".TheEgyptianswerefamiliarwiththeelectricphenomenaanditseffect.Thesheatfishcouldgenerateelectricshockswithseveralhundredvoltsinamplitude,soifacatchincludedsuchafish,thefishermenwereforcedtoreleaseallthecapturedfishbecauseoftheelectricshocktheyreceived. 03_kagemni_fishing.jpg Egyptian relief illustrating a fishing scene ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 ANCIENT TIMES TheancientGreeksusedthetorpedofish(electricray)tonumbthepainofoperationsandchild-birth.ThefirstknowntherapeuticapplicationofelectricitywritteninCompositionesMedicae(A.D.46):ScriboniusLargus(Romanphysician)usedthetorpedofishtocureheadacheandgoutarthritiswithsuccess. Galen(130-200)wasoneofthegreatestexperimentersoftheancienttimes.Studiedtherelationshipbetweenthenervoussystemandrespiration,carriedoutlesionexperimentsonthespinalcordofanimalsanddescribedseveralcranialnerves.Elaboratedthe"ventricular-pneumaticdoctrine”:theythoughtthat„animalspirits”,thatarisefrombrainventricles,areresponsibleforallofthefunctionsofthebody:thepneumaflowingthroughthehollownervesinducesmuscularcontractionsortransferssensationsbacktothebrain.Thisviewpointlastedformorethanathousandyearbecauseoftheinfluenceofthecatholicchurchandthe„three-celltheory”:alotofknowledgewasforgottenandpracticalexperimenting(likedissection)wasforbiddenatthattime. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 WILLIAM GILBERT (1544-1603) Englishphysician,physicistandnaturalphilosopher.Hestudiedmagnetism,andconcludedfromhisexperimentsthattheEarthismagneticandassumedthatthecentreoftheEarthisiron.Studiedthestaticelectricityusingamberandinventedthefirstelectricmeasuringinstrument,theelectroscope.GilbertsummarizedhisscientificworkinhisbookDeMagnete(AbouttheMagnet)whichwaspublishedin1600.Hecanbeconsideredasoneofthefathersofelectricityandmagnetism. William_Gilbert.jpg ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Gilberts_versorium_needle_electroscope.png 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 THE ELECTROSCOPE Theelectroscopeisaninstrumentformeasuringtheelectriccharge.ThefirstelectroscopewasinventedbyGilbertaround1600anditwascalledversorium.Itwasathinpivotedmetalneedlefixedinahorizontalpositiononawoodenscaffold.Theneedledeflectedwhenanobjectchargedwithstaticelectricitywasplacedneartheelectroscope.ThebasisofelectricchargedetectionistheCoulombelectrostaticforce.Theelectroscopecouldonlyusedwithstaticelectricityandelectrostaticmachines,whereenoughchargewasaccumulatedtodeflecttheneedle.Itgaveonlyaqualitativemeasurefromthemagnitudeofthecharge,throughtheamplitudeofthedeflection.JohnCantoninventedthepith-ballelectroscopein1754andthegold-leafelectroscopewasdevelopedbyAbrahamBennetin1787. Gilbert’sversorium (SylvanusPhillipsThompson:ElementaryLessonsinElectricityandMagnetism,1902,MacMillan&Co.,London,p.16,fig.11) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 ELECTROSTATIC GENERATORS Anelectrostaticgeneratorisadevicethatproducesstaticelectricity,whichisthebuildupofchargesonthesurfaceofobjects.Staticelectricitymeanshighvoltagewithlowcurrent.Electrostaticmachinestransformmechanicalenergyintoelectricenergyeitherbytriboelectriceffect(frictionmachines)orelectrostaticinduction(influencemachines).ThefirstfrictionmachinewasconstructedbyOttovonGuerickearound1663:itwasasulphurglobethatcouldberotatedandrubbedbyhand.IsaacNewtonchangedthesulphurtoglassandJ.H.Winklerchangedtherubbinghandtoleather.Lateron,collectingconductorswereconnectedtothefrictionmachinestostorethecharges.Theelectricsparkwasawellknownphenomenoninthelaboratoriesatthattime. Moreaboutelectrostaticmachines:link Elektrisiermaschine.jpg Frictionmachineusinga glassglobe (Hubert-François Gravelot: Die Elektrisierte, 1750) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 TIBERIUS CAVALLO (1749-1809) CavallowasanItalianphysicistandnaturalphilosopher.Heinventedthemultiplierin1770aninstrumentforamplificationofelectricchargesatalevelwhereitcouldbedetectedwithelectroscopes.Fourmetalplates,fromwhichthreewereinsulatedandoneconducting,wereplacedonawoodenboard.Threeoftheplateswerefixedontheboard,andonecouldbefreelymoved.Chargemultiplicationwasdonebymovingthisfreeplaterepeatedlybackandforthfromonefixedplatetotheother. Wilson’smachinewasaperfectedversionofCavallo’smultiplier,developedbyWilliamWilsonin1804. cavallos_multiplier.jpg Cavallo’s multiplier(A) and Wilson’s machine(B) (JohnGray:Electricalinfluencemachines,1890,Whittaker&Co.,London) A B ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 PIETER VAN MUSSCHENBROEK (1692-1761) Dutchscientist.HewasaProfessorofMathematics,Philosophy,MedicineandAstrology.Staticelectricitycouldbegeneratedbyfrictionmachinesthosetimes,butthemethodforthestorageofelectricitywasunsolved.In1746heinventedthefirstcapacitor:theLeydenjar.Hedippedawireinaglassjarfilledwithwaterandtriedtochargethewaterwithafrictionmachine.Hisassistantheldtheglassjarinoneofhishandsandbyaccidentallytouchingthewirewithhisotherhand,hegotanelectricshock.Hishandactednamelyasoneoftheplatesofthecapacitorwhiletheelectricallychargedwaterwastootherplate.TheGermanclericEwaldGeorgvonKleistalsoinventedtheLeydenjarindependentlyfromMusschenbroekin1744. Pieter_van_Musschenbroek.jpeg ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 THE LEYDEN JAR TheLeydenjarwasusedinmanyexperimentsinthefieldsofelectricityandalsoinelectrophysiologyandinelectrotherapy.Likementionedbefore,inMusschenbroek’sexperimenttheouterplateofthecapacitorwasthehumanhand,thedielectricwastheglassjarandthechargedwaterservedastheinnerplate.EarlyversionsoftheLeydenjarfollowedthisstructure.Chargingthewaterwaspossiblewiththehelpoffrictionmachinesthroughametalnailthatmadecontactwiththewaterinsidethejar. Early_Layden_jar.png Leydenjar W.JeromeHarrisonandCharlesA.White(1898)MagnetismandElectricity,5thEd.,BlackieandSon,UK,p.107,fig.64 ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 THE LEYDEN JAR ThetypicaldesignoftheLeydenjarconsistedofconductingmetalfoilscoatingtheouterandinnersurfacesofaglassjar.Thefoilswereseparatedfromeachotheratthemouthofthejar.Arodelectrodewasplacedinthejarandwasconnectedtotheinnerfoil.Thejarwaschargedbyanelectrostaticgeneratorviatheelectrode.Theouterfoilwasgrounded.Severaljarscouldbecombinedtoformabattery. leyden jar.jpg Leydenjar WalterLarden(1903)ElectricityforPublicSchoolsandColleges,LongmansGreen&Co.,NewYork,p.86 ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 USE OF STATIC ELECTRICITY Staticelectricity,sparksandthetriboelectriceffectoriginatingfromlaboratoriessoonbecameadailyentertainment.ButaccidentswithLeydenjarsandelectrostaticmachineshaveproventhatthehumanbodyisverysensitivetoelectricity,especiallythemusclesandthenerves.Shortlyaftertheseobservationstheelectricitywasuseduptotreatingpatients.Thiswasaprimitiveformofelectrotherapybasedonthetheory,thatthefluidsflowinginthenervesareelectricinnature:neuraldisorders,paralysisandmusclecrampscausedbyhydrophobiawere„cured”withthehelpofelectricity.Insomecasesitworkedverywell:forexampleaparalytichandofapatientalmostfullyrecoveredaftertheelectrotherapy. Alsomanyanimalexperimentswereconductedinthosedaystoobservetherelationshipbetweenthenervesandelectricity:forexamplethestimulationofthespinalcordcausedmuscletwitchesspreadingalloverthebody,buthadnoeffectontheheart. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 HENRY CAVENDISH (1731-1810) and the TORPEDO FISH Thetorpedofishes(orelectricrays)arecapableofproducinganelectricdischargeofuptoseveralhundredvoltsforself-defenseandforstunningtheirpreys.Theyhavetwoelectricorgansoneachsideoftheheadandaspecializedbrainlobe,theelectriclobe,forgeneratingelectricshocks.Theseanimalsturnupmanytimesinthehistory,forexamplesseethe„Ancienttimes”section. Cavendishcomparedtheelectricityretrievedfromelectricrayswithphysicalelectricity:hegottotheconclusion,thatthetwotypesofelectricityareidentical.Heconstructedamodelofthetorpedofish(torpedomarmorata)fromwood,leatherandLeydenjarsandcouldproducerealelectricshockswiththis„artificialtorpedo”.AccordingtoCavendish,thepropertiesoftorpedoessuggest,thateveryanimalcontains„electricalfluid”(electricalcurrent),andgottotheconclusionthatphysicalelectricphenomenaworkonthesamebasisastheelectricprocessesinthebodyoflivingorganisms. 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 RENÉ DESCARTES(1596-1650) Frenchphilosopher,mathematicianandphysicist.HistwowritingsLespassionsdel'âme(1649,PassionsoftheSoul)andLadescriptionducorpshumain(1647,TheDescriptionoftheHumanBody)areofbiologicalinterest.Forabout1500yearsthepopularviewwasthatnervesfunctionthroughtheactionofthe„animalspirits”or„pneumapsychikon”.Movementwasproducedbythese„movingspirits”,whichtravelleddownthehollownervesintothemuscles.Descartesthoughtthatthese„spirits”wereliquidsorgases.Inthiseraeveryphenomenawasexplainedthroughamechanicalviewpoint,sothehumanbodywasconsideredasacomplicatedmachinewherethenervousmechanismsfunctionlikehydraulicautomata.Ergothebodyfollowsthelawsofphysics. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Frans_Hals_-_Portret_van_René_Descartes.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 RENÉ DESCARTES(1596-1650) Descarteshadamodernview,butwasinmanyaspectswrong.Forexamplehesuggestedthepinealglandas„theseatofthesoul”.Thereasonofhischoicewasbecauseitwasknownthatthesoulisunitary,andunlikemanyareasofthebrainthepinealglandappearedtobeaunitarystructure.Anotherreasonforhischoice,thatthepinealglandwaslocatedneartheventricles,whichwereconsideredformanycenturiesthelocationsforimagination,cognition,andmemory.SoDescartesthoughtthatthecerebrospinalfluidoftheventricles,influencedbythepinealgland,flowedthroughthenervestomusclesandcontrolledthebody.WithhistheoryDescartesisolatedthemind(anon-materialentity)fromthebody(amachine)andcreatedthedualism. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Descartes_mind_and_body.gif 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 RENÉ DESCARTES(1596-1650) Becauseofthemanyanalogiesbetweenhumansandanimals,Descartessuggestedthathumanbehaviorcouldbestudiedthroughtheinvestigationofanimalbehavior.Forexampleheobservedthatbothhumansandanimalshavepinealglands.Butbecausehebelievedthatanimalsdonothaveasoul,heassumedthatanimalsdonotfeelpain.Thisresultedinthespreadofvivisection(thedissectionofliveanimals)inexperimentsthroughoutEurope. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 RENÉ DESCARTES(1596-1650) ThefirstcleardiscussionofareflexalsooriginatesfromDescartes:„ifthefireAisclosetothefootB,thesmallpartsofthisfire,which,asyouknow,moveveryquickly,havetheforcetomovethepartoftheskinofthefootthattheytouch,andbythismeanspullthesmallthreadC,C,whichyoucanseeisattached,simultaneouslyopeningtheentranceofthepored,e,wherethissmallthreadends…Theentranceoftheporeorsmallpassaged,e,beingthusopened,theanimalspiritsintheconcavityFenterthethreadandarecarriedbyittothemusclesthatareusedtowithdrawthefootfromthefire” (R.Descartes,DeHomine) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Descartes-reflex.JPG 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 JAN SWAMMERDAM(1637-1680) Dutchbiologist,studiedinsectsandcarriedoutexperimentsonmusclecontraction.Swammerdamwasthefirstwhoobservedanddescribedtheredbloodcells. Frogswerethebestsuitedanimalsforexperimentatthistimebecause”thenervesareveryconspicuousintheseanimals,andmaybeeasilydiscoveredandlaidbare.”Swammerdammadethefirstisolatedfrognerve-musclepreparation,whichbecamewidelyusedallovertheworldinneurobiologicalstudiesandhighschools. Ifthetheory-thatmusclecontractioniscausedbythe„animalspirits”flowinginthenerves–istrue,thanthevolumeofthemusclehastoincreaseoncontraction.Duringthedemonstrationofthishypothesis,Swammerdamexperiencedthatthecontactofasilverwireandabrasswireusedformovingthefrogsnervusischiadicus,irritatesthenerve-musclepreparationandgeneratesmusclecontraction. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 JAN SWAMMERDAM(1637-1680) Swammerdamcarriedoutthefirstelectrophysiologicalexperimentonafrognerve-musclepreparation.Thegastrocnemiusmuscleofthefrogwasplacedinaclosed,air-tightglasstube.Adropofwaterwasonthetopoftheglasstubeintheglasscapillary.Duringthemechanicalstimulationofthenervusischiadicusthevolumeofthecontractedmuscleshouldincreaseaccordingtothe„animalspirit”hypothesis,withthedropmovingupwards.Heexperiencedthecontrary:thevolumeofthemuscledecreasedduringcontractionornomovementofthewaterdropwasobserved.Swammerdamdidnotbelievehisownresults,suggestingthattheyweretheresultofanartifact. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 JAN SWAMMERDAM(1637-1680) Swammerdamshowedthatcuttingouttheheartofalivingfroghasnoeffectonitsabilitytomove,butifthebrainisremovedthereisnomoremovement. Heshowedinanotherexperimentthatnoconnectionisneededbetweenthemuscleandthebraintoevokemovements:touchingthenerveendsonadeadfrogwithascalpelcausedmusclecontraction(Hecalledthis„irritation”andthiswasoneformofexternalstimulation).ThiswasagaincontrarytoDescartes’theorywherethe„animalspirits”movedfromthebraintothemuscles. Theinitialdemonstrationsimplyinvolvedholdingthemusclethenstimulatingthenerve(Upperfigureontheright),butinhisnextexperimentheputthemuscleinaglasstubeandfixeditwithtwoneedlesthroughitstendons(Downfigureontheright). ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 JAN SWAMMERDAM(1637-1680) Hisexperimentwithafroghearthadtheresultthatduringcontraction„thedropofwateradheringneartheextremityofthetube(c),descendsinaveryremarkableandsurprisingmanner…thedropthusfallendown(d),will,ontheheart’sdilatingitselfagain,risetoitsformersituation(c).”ThiscompletelycontradictedDescartes’shypothesisagain. Swammerdamwasthefirstwhonoticedthedifferencebetweensensoryandmotornerves. Withhisexperimentaldesign,themovementofawaterdropinanairtightglasscapillary,heinventedtheplethysmograph,whichisadeviceformeasuringchangesinthevolumeoforgansorthewholebody. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 ALBRECHT VON HALLER(1708-1777) Swissanatomist,physiologist,naturalistandpoet.HebecameaProfessorofAnatomy,SurgeryandBotanyattheUniversityofGöttingenin1736.StudiedphysiologyinGöttingenandcarriedoutexperimentstoshowthat„sensibility”and„irritability”isapropertyoftheorganortissue.„Sensibility”meanstheabilitytoproducesensation,andafterhisfindingsonlyorganssuppliedwithnervesare„sensitive”.„Irritability”isthereactiontoastimulilikemusclecontractiongeneratedbyelectricstimulation.Hisscientificworkandresultsaboutthissubjectwerepublishedin1753inDepartibuscorporishumanisensibilibusetirritabilibus(Onthesensibleandirritablepartsofthehumanbody),whichlaterhelpedtounderstandmusclephysiology.WithhisfindingsHallerstatedthatnervesdonotplayaroleinmuscularmotion,incontrasttothepopulartheoryof„animalspirits”wheretheflowof„nervousfluid”fromthebrainthroughthenervesproducedthemovements. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Albrecht_von_Haller_1736.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 LUIGI GALVANI (1737-1798) Italianphysicianandphysicist.In1762hebecameaperformerinanatomyontheUniversityofBologna.In1775hebecamehereaProfessorofAnatomyandObstetrics.Galvanistartedhisfamousfrogexperimentsintheearly1780’s:the„animalelectricity”wasdiscoveredwithelectricalstimulationofthefrognerve-musclepreparation.HisscientificworkissummarizedinhisbookDeviribuselectricitatisinmotumuscularicommentarius(CommentaryontheEffectofElectricityonMuscularMotion),publishedin1791.Hissecondworkonanimalelectricity,Trattatodell’ArcoConduttore(TreatiseontheConductingArc)waspublishedin1794.In1796GalvaniwasdismissedfromhisuniversitypositionsbecauseherefusedtotakeaciviloathtothenewNapoleonicrepublicforpoliticalandreligiousreasons. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Luigi_Galvani,_oil-painting.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 LUIGI GALVANI (1737-1798) Galvanicanberegardedasthefounderofelectrophysiology.Hemadehisexperimentsmainlyonfrogs,becausetheirmuscleskeptoncontractingforalongtimeafterdeath.Hisfamousexperimentperformedonthe26thJanuaryof1781isdefinedasGalvani’s„firstexperiment”.Heleftanerve-musclepreparationonthetablewithafrictionmachine.(atthattimejuststaticelectricitywasknown,whichchangedsoonwiththeinventionofdynamicelectricitybyVolta)Hisassistantaccidentallytouchedthenerveofthepreparationwithascalpelexactlyatthesametimewhenthefrictionmachinegeneratedaspark.Asaresultthefrogmusclecontracted.Thismeantthatelectricityfarfromthenervecanalsohaveaneffectifaconductivemediumispresent(theassistant).Themuscularcontractiondependedonwhetherthemachinesparkedorthecontactwasdonewithaninsulatedscalpel.Latertheyconnectedthefrictionmachinewithametalwiretothefrogleg:thecontractionofthemuscleappearedagainasexpected. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 Galvani’sfrogexperiments(L. Galvani: De viribus electricitatis in motu musculari commentarius, 1791) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY galvani2.jpg galvani3.jpg galvani1.jpg galvani4.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 LUIGI GALVANI (1737-1798) InanotherexperimentGalvanihookedupthefroglegsonaninsulatedmetalwireoutsideofthehouse.Astormwasjusttobreakout,andalightningstrikehittheconductingwirecausingthecontractionofallofthemusclesofthepreparations.ThiswasthedemonstrationthatnaturalelectricitydiscoveredbyBenjaminFranklin(1706-1790)canalsoinitiatemuscularcontractions. Galvanidevelopedoneofthemostmodernlaboratoriesinhisownhouse:itwasequippedwiththebestinstrumentsforelectricalresearchknownthattime.Electrostaticmachines,Leydenjars,Aepinus’condenserandrecentlyinventeddevicesliketheelectrophoruscouldalsobefoundinhislab. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 LUIGI GALVANI (1737-1798) Theterm„animalelectricity”(alsooftenreferredasgalvanism)comesfromGalvani.HecomparedthemusclefiberstoLeydenjars.Accordingtohisopinion,electricityisflowingfromthebrainthroughthenervestoeveryorgan,sotothemusclestoo.Themusclesstorethiselectricityandwhenastimulusgeneratesanelectricdischarge,theexcitablemusclescontract. ThistheorywasattackedbyhiscontemporaryAlessandroVoltain1792:afamouscontroversybeganbetweenthetwoscientistsabouttheexistenceof„animalelectricity”,whichwascontinuedbyGalvani’snephewGiovanniAldiniafterhisdeathin1798.Voltaclaimedthatthemuscularcontractionisjustduetotheinteractionbetweentwodifferentmetals,thatgenerateagalvaniccell. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 ALESSANDRO VOLTA (1745-1827) Italianphysicist.In1774hebecameProfessorofPhysicsattheRoyalSchoolofComoandin1779hebecameProfessorofExperimentalPhysicsattheUniversityPavia.In1775heimprovedtheelectrophorus(inventedbyJohanCarlWilckein1762),adevicethatproducesstaticelectricchargeviatheprocessofelectrostaticinduction.Voltadiscoveredmethaneandstudiedtheelectricalcapacitance.HebecamefamiliarwithGalvani’s„animalelectricity”in1791andshortlyobservedthatelectricityisalwaysflowingbetweentwometalsseparatedbyanelectrolyte.ThefrogpreparationservedastheelectrolyteinGalvani’sexperiment,andbecausethemuscleisanexcitabletissuetheelectriccurrentforceditcontract.SoaccordingtoVolta’sfindingsthereisno„animalelectricity”. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Alessandro_Volta.jpeg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 ALESSANDRO VOLTA (1745-1827) In1800Voltainventedthevoltaicpile,thefirstelectricbattery,andnameditgalvaniccellinhonorofGalvani.Thedeviceconsistedoftwodifferentmetaldiscs(forexamplebrassandzinc,butsilverwasalsooftenusedinplaceofbrass),thesewereplacedaboveeachotherinanalternatingpatternwithcardboardssoakedinsaltwaterbetweenthemetalpieces.Thewetcardboardsservedastheelectrolyteandthesaltwatercouldbereplacedwithsulphuricacid.ThevoltaicpileproducedelectriccurrentcontinuouslyandforalongtimecontrarytotheLeidenjarorthestaticelectricityinducedhigh-power,flashlikedischargesofelectriccondensationdevices. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 ALESSANDRO VOLTA (1745-1827) SoVoltafiguredoutthattwodifferentmetalsinthepresenceofawetmedium,likethemuscleofthefrog,generatemuscularcontractions.Inhisopinionjusttwodifferentmetalsandanelectrolyteisneededtoproduceelectricity.Themuscleofthefrogisonlyawetmedia,whichdetectsandreactstoelectricitywithcontractionbecauseofitsexcitability.Themuscleitselfdoesnotgenerateelectricity.Thereisno„animalelectricity”,justthetwometalsareproducingtheelectriccurrent.Thisphenomenoniscalledbimetallicelectricity. Galvani’sriposte:provedthat„animalelectricity”existsandisarealphenomenon.Hecutthroughthespinalcordoffrogsandputoneofthepreparedlegmuscletothelesionedendofthespinalcord.Whenthefreeendofthemuscletouchedthemarrow,itcontracted.WiththisexperimentGalvaniunwittinglydiscoveredthephenomenonofthe„lesioncurrent”. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 ALESSANDRO VOLTA (1745-1827) Manyexperimentsonelectricstimulationofthebrainwerecarriedoutwiththevoltaicpileatthistime.Insects,frogs,andmammalswereusedtogeneratemuscularcontraction(Humboldt,Cabanis),butwithoutsuccessbecausethebatteryinventedbyVoltaproducedsmallcurrents,andprobablytheexperimenteravoidedthemotorcortexandtheotherbrainstructurescapableofevokingmovements. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 The voltaicpile(A. Volta, On the Electricity Excited by the Mere Contact ofConducting Substances of Different Kinds, 1800) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY voltaic pile.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 GIOVANNI ALDINI(1762-1834) Italianphysicist,nephewandassistantofGalvani.HebecameProfessorofPhysicsinBolognain1798.AldinicarriedoutexperimentswheretheprinciplesofGalvani(animalelectricity)andVolta(bimetallicelectricity)wereusedtogether.Hewasthefirstwhoperformedelectricstimulationonthehumanbrain.ContinuedthescientificdebatebetweenVoltaandGalvanifromtheexistenceof„animalelectricity”afterGalvani’sdeath.Demonstratedthatmuscularcontractioninfrogscanbeobtainedwithonemetalonly(heusedpurifiedmercury)orwithouttheuseofanymetals.Hetreatedandcuredpatientssufferingfromvariousmentaldisorders(likemajordepression)withthehelpoftranscranialelectriccurrentadministration. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Giovanni_Aldini.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 GIOVANNI ALDINI(1762-1834) Hemadeexperimentsontheheadsandtrunksofrecentlydiedcows,sheep,dogsandhorses.Moistenedtheinsideoftheearsorthenasalcavitywithsaltwaterandputoneofthemetallicwireshereandtheotherwiresomewhereinthebrain.Twitchesofthefacialmusclesandthemusclesoftheextremitieswereobservedduringclosingoropeningtheelectricarc.Hestimulatednotjustonthesurfaceofthebrain,butenteredalsotothedeeperregions.Stimulatingdeepincreasedtheamplitudeofmusclemovements.Carriedoutexperimentontheheadsandbodiesofexecutedcriminals:twitchingoffacialmusclesortheconvulsionofthecorpsewasvisible.Hismostfamousdemonstrationin1803ontheexecutedmurdererGeorgeFosterhadverydramaticresults:“thejawbegantoquiver,theadjoiningmuscleswerehorriblycontorted,andthelefteyeactuallyopened.”Afterplacingonerodtotherectum,themovementsofthedeadbodywere“somuchincreasedasalmosttogiveanappearanceofreanimation.” ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 GIOVANNI ALDINI(1762-1834) Forhisexperimentsheusedvoltaicpileswhichwereconstructedfromcopperandzincdisks.Oneofthesegalvaniccellsconsistedof100copperandzincpieces.Heprovedthatstimulatingthelefthemisphereleadstocontralateralmovements. TravelledthroughoutEuropetopopularizegalvanismandthetheoryof„animalelectricity”andalsotheusefulnessoftranscranialstimulationinmedicine.In1804hepublishedhisbookEssaithéoriqueetexperimentalsurlegalvanisme(Theoreticalandexperimentalessayongalvanism)whichcontainsthedescriptionofhisexperimentsand10beautifulandinformativeplatesdrawnbyPecheux.Unfortunatelyhisfindingsgotlostorwereignoredbythecommunity,andhisexperimentswerenotcontinuedbyanyone.ElectricstimulationofthebrainwerediscoveredagainonecenturylaterbyGustavFritschandEduardHitzig. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 Early„electrotherapy” byAldini(AldiniJ.: Essai théorique et experimental sur le galvanisme,1804) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY aldini3.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 Animalexperiments(AldiniJ.: Essai théorique et experimental sur le galvanisme,1804) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY aldini3.jpg aldini7.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 38 Experimentsonexecutedcriminals(AldiniJ.: Essai théorique et experimental sur le galvanisme,1804) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY aldini3.jpg aldini9.jpg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 EARLY ELECTRIC MEASURMENT DEVICES Agalvanometerwasaninstrumentfordetectingandmeasuringelectriccurrent.JohannSchweigerbuiltthefirstgalvanometerin1820:itwasacompasswithacoilofwiresaroundit.Thisearlydeviceswerealsocalled„multipliers”becauseofthemultipleturnsofwire.Later,galvanometerswereconstructedwithtwomagnets,tobecomeindependentoftheEarth’smagneticfield.Thiswerecalled‘astatic’galvanometers.WilliamThomson(LordKelvin)inventedthemirrorgalvanometer(patentin1858),wherethemagnitudeofthecurrentswerecalculatedfromthedeflectionofalightbeamdirectedtoamirrormovedbythemagnetsattachedtoit.ThestringgalvanometerwasdevelopedbyWillemEinthovenin1901:thecurrentsweredetectedwithathinandlongsilvercoatedquartzfilamentandtheinstrumentwasthefirstpracticalECG.AnothersolutionformeasuringsmallcurrentswasthecapillaryelectrometerinventedbyGabrielJonasLippman:thisdevicecouldalsobeusedfordetectingthesmallcurrentsoftheheart. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 CARLO MATTEUCCI (1811-1868) Italianphysicistandphysiologist.BecametheProfessorofPhysicsattheUniversityofPisain1840.MatteuccifollowedtheworkofGalvaniandhis„animalelectricity”.Startedhiselectrophysiologicalexperimentsin1830andcontinuedtheseuntilhisdeath.ProvedwithasensitivegalvanometerinventedbyNobili,thattheinjuredtissuegeneratesacontinuouslyflowingelectriccurrent.Serialstackingofmuscles,thatforma„musclepile”produceagreatercurrent,thananindividualmuscle,samewayasputtingmoremetaldiskstoavoltaicpilegeneratesbiggercurrents.Hedemonstratedsparklesbyputtingatorpedofishbetweentwometalplates.Withhisexperimentsheprovedunequivocally,thatthelivingorganismcantrulygenerateelectricsignalshoweveritwasnotlocatedtothecentralnervoussystem. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Carlo_Matteucci.jpeg 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 CARLO MATTEUCCI (1811-1865) Heusedfrogpreparationstohisexaminations.Inoneofhisexperimentshetouchedtheinjuredmuscleofafrognerve-musclepreparationwiththenerveendingofanotherpreparation.Themuscleofthelatterpreparationcontracted.Hestatedwiththehelpofagalvanometer,thatacurrentisflowingbetweentheinjuredanduninjuredsurfacesofthemuscle,laterthisphenomenonwascalled„currentofinjury”.Theanotherfrogpreparation„sensed”thiscurrentandgeneratedamuscularcontraction.Hecalledthisfrogpreparation„rheoscopicfrog”andusedasanelectricsensorinotherexperimentslikeinthedemonstrationofthepresenceofelectriccurrentintheheartateveryheartbeat. Matteucciwrotemanypapersonhiselectrophysiologicalinvestigations:forexampletheTrattatodeifenomenielettrofisiologicideglianimali(Treatiseofelectrophysiologicalphenomenaoftheanimals)waspublishedin1844andelevenmemoirscanbefoundinthePhilosophicalTransactionsfrom1845-1861withthetitleElectro-PhysioligicalResearches. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 JOHANNES MÜLLER (1801-1858) Germanphysiologistandcomparativeanatomist.MüllerbecameaProfessorofPhysiologyattheBonnUniversityin1830,butsoonwenttotheHumboldtUniversityofBerlin(1833)alsoasaProfessorofPhysiology.HewasthementorofgreatscientistsasCarlLudwig,EmilduBois-Reymond,HermannvonHelmholtz,TheodorSchwannandFriedrichGustavJacobHenle.Müller’sfamousworkHandbuchderPhysiologiedesMenschen(HandbookofHumanPhysiology,1833–1840)becametheleadingtextbookinthesubject.Contributedtomanyareasofphysiology,especiallytoneurophysiology.Hestudiedthecranialnerves,acceleratedtheunderstandingofhearingandspeech,buthismostimportantworkwasaboutthemechanismsofsenses. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 43 JOHANNES MÜLLER (1801-1858) OneofMüller’sgreatexperimentswasthatresultedinthedistinguishingbetweensensoryandmotornerves.Bymechanicallyorelectricallystimulatingtheanteriorrootsoffrogsheobservedmovementintheextremities,whichwasnotpresentincaseofthestimulationoftheposteriorroots.Hecarriedoutananotherexperimentthatsensoryandmotornervesareseparate:cutthroughtheposteriorrootsofnervesfromalimboffrogsanddogs.Thelimbsbecameinsensible,butmovementswerefurtherobservable.Howeverthelesionoftheanteriorrootsresultedinparalyzedlimbswhichhavenotlosttheirsensibility. In1844Müllerdidthefollowingstatement:„Probablywewillneverhavethemeanstomeasurethespeedofthenervousaction,sincewelack,inordertoestablishcomparisons,theseimmensedistanceswherebywecancalculatethespeedoflight,which,underthisrespect,hassomerelationwithit.”AfewyearslaterhispupilHermannvonHelmholtzmeasuredthenerveconductionvelocityofthefrognervusischiadicus. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 JOHANNES MÜLLER (1801-1858) Hisresearchesaboutthesensesandstimulation-sensationrelationshipresultedintheformulationofthe„lawofspecificnerveenergies”: „Thesamecause,suchaselectricity,cansimultaneouslyaffectallsensoryorgans,sincetheyareallsensitivetoit;andyet,everysensorynervereactstoitdifferently;onenerveperceivesitaslight,anotherhearsitssound,anotheronesmellsit;anothertastestheelectricity,andanotheronefeelsitaspainandshock.Onenerveperceivesaluminouspicturethroughmechanicalirritation,anotheronehearsitasbuzzing,anotheronesensesitaspain...Hewhofeelscompelledtoconsidertheconsequencesofthesefactscannotbutrealizethatthespecificsensibilityofnervesforcertainimpressionsisnotenough,sinceallnervesaresensitivetothesamecausebutreacttothesamecauseindifferentways...(S)ensationisnottheconductionofaqualityorstateofexternalbodiestoconsciousness,buttheconductionofaqualityorstateofournervestoconsciousness,excitedbyanexternalcause.” ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 CARL WILHELM LUDWIG (1801-1858) Germanphysicianandphysiologist.HebecameaProfessorofPhysiologyin1842andaProfessorofComparativeAnatomyin1846.Heinventedthekymographin1847,adeviceusedforrecordingthebloodpressure.Lateritwasusedbyexperimentalphysiologistsforrecordingvarioustimerelatedeventsasresponsetimes,musclecontractionortuningforkvibration.Thekymographconsistedofarotatingdrumholdingarecordsheetwhichwasusuallyasmokedpaper.Astyluscontactedthesheetandrecordedthesignals. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY img5597.jpg Ludwig’skymograph(Éliede Cyon: Methodik der physiologischen Experimente und Vivisectionen, 1876) 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 HERMANN L. F. VON HELMHOLTZ (1820-1894) Germanphysicianandphysicist.HebecameaProfessorinPhysicsattheUniversityofBerlinin1871.Helmholtzworkedonmanyareasofthemodernsciencewithsignificantresults.Hestudiedthevisionandeye,andpublishedtheHandbuchderPhysiologischenOptik(HandbookofPhysiologicalOptics)in1867whichbecameafundamentalreferenceworkinthesubjectofvisionandincludedtheoriesoncolorvision(trichromatictheoryofcolorvision),visualperceptionandspatialvision.Inventedtheophthalmoscope,aninstrumentusedtoexaminethehumanretina.Healsocontributedtothefieldofhearingwithstudiesaboutthesensationoftone,theperceptionofsoundandtheorganofCorti.Inphysicsthediscoveryofthelawofconservationofenergymadehimwidelyknown. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Hermann_von_Helmholtz!!!.jpg Tantárgy neve angolul: Fejezet címe angolul 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 HERMANN L. F. VON HELMHOLTZ (1820-1894) Hismaincontributiontoneurophysiologywasthemeasuringofthenerveconductionvelocityofthefrogin1850,whichwasstatedimpossiblebyhistutorJohannesMüller.Thecourseoftheinterestingexperimentwasthefollowing:Helmholtzstimulatedthenervusischiadicusofthefrogwithstaticelectricitywhichresultedinthecontractionofthegastrocnemiusmuscle.Themusclewastieduptothestylusofakymographsothecontractioncausedadeflectiononthesmokedpaper.Therotationofthekymographwasstartedbyaspringandasmalldeviceclosedtheelectriccircuitintheappropriatetime,afterthespringreleasedthekymograph.Thespringstoppedthekymographafteroneturn. Tomeasurethenerveconductionvelocity,Helmholtzstimulatedthenerveattwodifferentpoints:firstfurtherfromthemuscle,thanclosertoit.Whenstimulationwascarriedoutcloser,themuscularcontractionhappenedearlierandwhenstimulatedfurther,asmalldelaywasobservableinthecontraction. Tantárgy neve angolul: Fejezet címe angolul 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 HERMANN L. F. VON HELMHOLTZ (1820-1894) Afterthathehadonlytomeasurethedistancebetweenthetwostimulationpointsandthetimedifferencebetweenthetwocontractions.Themeasuringofthetimeonthekymographwasachievedwiththehelpofsinewavedrawnbya100Hztuningfork.Thisresultedina10mstimescale.Hegottheconductionvelocitybycalculatingthequotientofthedistanceandtime.Forthemotornerveofthefrogthisvaluewasapproximately30m/s.Laterhemeasuredtheconductionvelocityofthesensorynervestoo,andagotaresultaround50-100m/s.Hemeasuredtheconductionvelocityalsoonhumansubjects.Anotherfindinghemade,thattheconductionvelocitydependsonthetemperature:colddecreasesthevalues,heatincreasesit. Publishingtheresultswerenotaneasytask:neitherMüller,norHumboldtacceptedhisfinding,butfinallyhisfriendDuBois-Reymondhelpedhim.SoonafterMüllerandalsoHumboldtadmittedtheaccuracyofhismeasures,whichroughlyspeaking,holdoutnowadaystoo. 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 EMIL DU BOIS-REYMOND (1818-1896) Germanphysicianandphysiologist.Hecanberegardedasthefounderoftheexperimentalelectrophysiology.Discoveredthenerveactionpotential.HisbookUntersuchungenüberthierischeElektricität(ResearchesonAnimalElectricity)appearedin1848.HestartedhisworkonelectrophysiologyandbioelectricityafterreadingtheessayofCarloMatteuccigotfromhismentorJohannesMüller.HerepeatedMatteucci’sexperimentsandconfirmedsomeofhisresults,butinmanycasesduBois-ReymondhadproventhatMatteucciwaswrong.Heimprovedthegalvanometersusedformeasuringthecurrentsoffrognerve-musclepreparationsandusedinducedcurrentforstimulation.TheinductioncoilinventedbyMichaelFaradaywasusedfirstinmedicalapplicationsbyduBois-Reymond.ThiswascalledFaradaystimulation.Theterms„electrotonus”and„stimulation”alsocomesfromhim. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 EMIL DU BOIS-REYMOND (1818-1896) LikeMatteucci,healsodiscoveredthe„actioncurrent”orwithanothertermthe„currentofinjury”.(butthetermcomesfromhisstudentHermannLudmar)DuBois-Reymondnamedthisphenomenon,-wheretheharmedsurfaceofthefrogmusclewasnegativeaccordingtotheunharmedsurface-„negativevariation”(„NegativeSchwankung”)Hefoundthisprocessalsoinnerves.This„negativevariation”,whichisactuallythewell-knownactionpotential,travelsthroughthewholenervewithoutenergyloss,sotheythoughtthatthisphenomenonisidenticaltothe„animalelectricity”discoveredlongago.Hemeasuredthemembranepotentialfromtheharmedsurfacewithmacromethods. Hewasthefirstwhomentionedthatsomechemicalprocesscouldbethereasonofthedelayoftheactionpotentialwhenadvancingfromthenerveendingtothemuscle. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 51 Britishscientist,physicianandphysiologist.Developedmanypracticalneurosurgicaltechniquesasthebonewax,theskinflaportheHorsley-Clarkeapparatus.ThelatterwasdevelopedtogetherwithRobertH.Clarkein1908andwasusedtoperformstereotacticsurgery.Withthismethodpreciselocalizationofeachbrainstructurecouldbeachievedwiththehelpofnumericalcoordinatesandastereotacticbrainatlas.TheimprovedversionsoftheHorsley-Clarkeapparatus,whicharenowadayscalledstereotaxicframes,arewidelyusedinanimalexperimentsandinhumanneurosurgery.Horsleywasalsoaverytalentedneuroscientist:hestudiedthebrainfunctionsofhumansandanimals,concentratingmainlyonthecerebralcortex.Hewasthefirstwhousedintraoperativeelectricalstimulationofthecortextolocalizetheepilepticfociinhumans. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Victor_Horsley.jpg SIR VICTOR ALEXANDER HADEN HORSLEY(1857-1916) 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 52 EDUARD HITZIG (1839-1907) GUSTAV FRITSCH (1838-1927) HitzigwasaGermanneurologistandneuropsychiatristandFritschaGermananatomistandphysiologist.MorethanahalfcenturyafterAldini’sforgottenexperimentstheyrediscoveredthemovementsevokedwithbrainelectricalstimulation.Theystudiedtherelationshipbetweentheelectriccurrentandthebrainontheexposedcerebralcortexofunanesthetiseddogs.Theyobservedthatthestimulationofcertainpartsofthecerebrumcausedinvoluntarymuscularcontractionsofspecificpartsofthedog'sbody.Withthisdiscoverytheylocalizedthemotorcortexwhichisthebrainarearesponsibleforvoluntarymovements.TheypublishedtheirfindingsintheArchivfürAnatomie,PhysiologieundwissenschaftlicheMedicinwiththetitleUeberdieelektrischeErregbarkeitdesGrosshirns(OntheElectricalExcitabilityoftheCerebrum)in1870. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Hitzig.JPG 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 53 RICHARD CATON (1842-1926) Britishphysicianandscientist.CatonbecameaProfessorofPhysiologyin1881attheVictoriaUniversity.Hewasthefirstwhorecordedbioelectricsignalsfromthecerebralcortex.Toachievethis,hedevelopedfurtherthetechniquesofDuBois-Reymondin1875andrecordedelectricpotentialsfromthebrainwithThomson’smirrorgalvanometer.Forhisexperimentsheusedcats,monkeysandrabbits.Afteropeningtheskullandremovingthedura,electrodeswereclampedtotheskulloftheanaesthetizedanimalstoavoidtheirdisplacementduringmovements.Oneelectrodewasplacedovertheareaunderstudyandtheothersomewhereonthesurfaceofthebrainorontheskull.Afterthesurgeryanimalswereallowedtorecoverconsciousness.WiththemovingofthedifferentbodypartsoftheanimalsCatoncouldrecordelectricalresponsesintheappropriatebrainareas.HeusedDavidFerrier’s(1843-1928)mapfromthemonkeycerebralcortextodeterminethelocationoftheelectrodes. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 54 RICHARD CATON (1842-1926) Theobservedvariationofpotentialswereindependentfromtheheartbeat,respirationandfromouterstimuli.Indyinganimalsthedegreeofdeflectionsdecreasedandsoonlateritceased.Accordingtohim,themeasuredelectricalpotentialsweregeneratedbytheelectropositivityofthebrainsurfaceandbytheelectronegativityoftheregionsunderthecortex. Healsorecordedpotentialsshiftsbygivingstrongstimulustotheanimals.Forexamplebyilluminatingtheretinaofthelefteyewithbrightlightheobservedelectricalpotentialchangesintheposteriorpartoftherighthemisphere. CatonpublishedhisfindingsintheBritishMedicalJournalin1875withthetitleTheelectricalcurrentsofthebrain.Twootherpublicationsfollowedthisoneandafterthesehestoppedhisstudiesonthebrainandnevercontinueditagain.Hisdiscoveriesdidnotbecamewidelyknown,somanyscientistsrediscoveredhisfindingsafewyearslater. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 55 BRAIN ELECTRIC POTENTIALS In1876VasiliYakovlevichDanilevsky(1852-1939)cametosimilarresultsindependentfromCaton,withexperimentsondogsparalyzedwithcurare. AdolfBeck(1863-1942)wasalsounawareofCaton’sresultsandrepeatedthemadecadelater.Hestudiedthespontaneouselectricactivityofthebrainandobservedthatthesespontaneouswavesarenotuniform,theycanbeseparatedindifferentgroups.Beckstatedthatalsohumanbrainfunctionscouldbestudiedwithelectrodesplacedonthescalp,butthenecessaryamplificationtechnologywasnotyetavailable.Beckpublishedhisresultsin1890intheZentralblattfürPhysiology.Soonafterhispaperappeared,asealedletterwasopenedontheAcademyofViennasealedbyFleischlvonMarxowin1883.IntheletterMarxowwrotethathealreadymadeasimilardiscoveryaboutbrainpotentialsyearsago.Hedidnotpublishhisobservations,butwiththeletterheprovedhispriority.In1891Catonclearedthesituationaboutthepriority:hementionedhisreportpublishedin1875aboutbrainelectricalcurrents. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 56 HANS BERGER (1873-1941) Austrianpsychiatrist.BergerbecameaProfessorinPsychologyin1919attheUniversityofJena.Herecordedthefirstbioelectricsignalsfromthebrainofahumanin1924.Hissubjectwashis15yearoldsonKlaus.HenamedtherecordingsElectroenkephalogram(EEG).PublishedapaperabouthisfindingsintheArchivfürPsychiatrieundNervenkrankheitenwiththetitleÜberdasElektroenkephalogrammdesMenschenin1929.Discoveredandnamedthefirstbrainrhythms:thealphaactivityappearsinarelaxed,butalertstate,whentheeyesareclosed.Itdisappearswhencountingorothermentalactivitiesareperformed.Thefrequencyrangeofthealpharhythmisfrom8to12Hzandcanberecordedwiththebestqualityfromtheoccipitalregionofthebrain.Hegavethename„alphawaves”becausethesewasthefirstwaveformsisolatedfromthehumanEEG,butforhishonoralphawavesarealsocalledBerger-rhythm. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 57 HANS BERGER (1873-1941) Betawaveshavealoweramplitudebutahigherfrequency(12-30Hz)comparedtotheBergerrhythmandarerelatedtomentalconcentrationandtostartlereactionsaccordingtoBerger. Heusedsilverwiresorsilverfoilelectrodesplacedonthescalpofthesubjects,oneelectrodeactingasareferenceandtheotherastheactiveelectrode.Usuallyoneoftheelectrodeswasplacedatthefrontofthehead(reference)andtheotheratthebackovertheoccipitallobe.AsarecordingdevicehetriedfirstLippmann’scapillaryelectrometerwithpoorresults,afterthatheswitchedtothestringgalvanometer.LaterheusedadoublecoilSiemensgalvanometer. HestudiedtherelationshipoftheEEGandbraindiseaseslikeepilepsy,Alzheimer’sdiseaseorsclerosismultiplex.Inotherexperimentshefoundthatalphawavesdiminishedduringsleeporduringgeneralanesthesia. In1941afterthoughtimescausedbytheNazis,Bergercommittedsuicide. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 58 WILLIAM GREY WALTER (1910-1977) Americanneurophysiologist.ImprovedtheEEGinventedbyHansBerger,allowingWaltertodetectmanyofthewell-knownbrainwavesfromthealphatothedeltarange.Withthisdevicehemadeanumberofdiscoveriesforexamplehecouldusethedeltawavestolocatebraintumors.Inthe1960shediscoveredthecontingentnegativevariation(CNV)orreadinesspotential.Developedthefirstbraintopographymachine(alsocalledtoposcope)incollaborationwithHaroldW.Shipton,anelectronicengineer.ThetoposcopedisplayedthespatialorganizationoftheEEGactivityinanewway.Itconsistedofanarrayofsmallcathoderaytubesconnectedtohighgainamplifiers.Hewasalsointerestedinrobotics:theMachinaSpeculatrixwasoneofthefirstelectronicautonomousrobot,constructedbyWalter. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY handb2 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 59 INVENTIONS IN THE 20TH CENTURY Thediscoveriesontheelectricphenomenaofthebraincametoasuddenstopattheendof19thcentury,andneededthedevelopmentofnewtechnologiesandtechniquestoproducenewstrikingresults.Heresomeexamplesofinventionswhichhelpedelectrophysiologytoregainitsleadingroleinthefieldofscience. KarlFerdinandBraundevelopedthecathoderaytubeoscilloscopein1897.LeedeForestinventedin1906thevacuumtube,whichcouldamplifytheweakbioelectricsignalsofbrain.ThefirsttransistorwasdevelopedbyJohnBardeenandWalterBrattainin1948attheAT&T’sBelllabs.Thefieldeffecttransistor(FET)madeitpossibletobuildminiaturized,reliable,portableandmuchcheaperinstruments.Later,withtheinventionoftheMOS(metaloxidesemiconductor)transistorandtheintegratedcircuittechnology,theEEGmachinesandotherscientificdevicesbecameaffordablebysmallerlaboratoriestoo. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 60 NOBEL PRIZES IN ASSOCIATION WITH BIOELECTROMAGNETIC PHENOMENA ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Year Name Nationality 1901 Jacobus van't Hoff The Netherlands 1903 Svante Arrhenius Sweden 1906 Camillo GolgiSantiago Ramón y Cajal ItalySpain 1920 Walther Nernst Germany 1924 Willem Einthoven The Netherlands 1932 Edgar Douglas AdrianSir Charles Sherrington BritainBritain 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 61 NOBEL PRIZES IN ASSOCIATION WITH BIOELECTROMAGNETIC PHENOMENA ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Year Name Nationality 1936 Sir Henry Hallet DaleOtto Loewi BritainBritain 1944 Joseph ErlangerHerbert Spencer Gasser U.S.U.S. 1949 Walter Rudolf Hess Switzerland 1961 Georg von Békésy U.S. 1963 Sir John EcclesAlan Lloyd HodgkinAndrew Fielding Huxley AustraliaBritainBritain 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 62 NOBEL PRIZES IN ASSOCIATION WITH BIOELECTROMAGNETIC PHENOMENA ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Year Name Nationality 1967 Ragnar Arthur GranitHaldan Keffer HartlineGeorge Wald FinlandU.S.U.S. 1968 Lars Onsager U.S. 1970 Julius AxelrodSir Bernard KatzUlf von Euler U.S.BritainSweden 1981 David Hunter HubelTorsten Nils Wiesel Roger WolcottSperry U.S.Sweden U.S. 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 63 NOBEL PRIZES IN ASSOCIATION WITH BIOELECTROMAGNETIC PHENOMENA ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY Year Name Nationality 1991 Erwin NeherBert Sakmann GermanyGermany 2000 Arvid Carlsson Paul Greengard Eric Kandel U.S.U.S. U.S. 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 64 CAMILLO GOLGI (1843-1926) S. RAMÓN Y CAJAL (1852-1934) TheyreceivedtheNobelPrizeinPhysiologyorMedicinein1906fortheirstudiesonthestructureofthenervoussystem.ThiswasthefirstsharedNobelPrize. Golgiinventedthesilver-staining,animpregnationmethod,whichrandomlystainscellsinthenervoustissue.Thetracedblackneuronswerewellseparablefromtheyellowbackground.GolgidiscoveredtheGolgitendonorganandGolgiapparatusinthecells.TheGolgicellsinthecerebellumwerenamedalsoafterhim. Cajalwasagreatsupporteroftheneurondoctrine,whichstatedthattheneuronisthefunctionalunitofthenervoussystem,thatbuildsupfromthesediscrete,individualcells.Golgi’ssilver-stainingwasaverygoodprooftothetheory,nonethelessthatGolgiheldopposedviews:hethoughtthatthenervoussystemisahugenetwork,wherecontinuityisbetweeneverypartofthesystem. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 65 WILLEM EINTHOVEN (1860-1927) EinthovenreceivedtheNobelPrizeinMedicinein1924forinventingthefirstpracticalelectrocardiogram(1903).FirstelectrocardiogramsbasedonLippmann’scapillaryelectrometerwereveryinaccurateandhadverylittleclinicalsignificance.Einthoven’sECGrecorderusedastringgalvanometerwhichwasmuchmoresensitivethanthecapillaryelectrometer,butwasfarnotsocomfortablethanmodernECGs:thesubjectshadtoimmersetheirhandsandlegsintocontainersofsaltwater.TheECGwasrecordedfromthesaltsolutions. EinthovennamedthedeflectionsoftheECG:thelettersP,Q,R,S,Twereassignedtothewaves.Hedescribedtheelectrocardiographicfeaturesofanumberofcardiovasculardisorders. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 66 EDGAR DOUGLAS ADRIAN (1889-1977) SIR CHARLES SHERRINGTON (1857-1952) TheywontheNobelPrizeinPhysiologyfortheirworkonthefunctionofneuronsin1932. Adrianstudiedthepropertiesofthepropagatingelectricimpulsesonfrognerve-muscleswiththehelpofacapillaryelectrometerandacathoderaytube,whichamplifiedthebioelectricsignals.Heinvestigatedthesensoryandthemotornervesandfoundthatthestrengthandquantityofthestimulusisexpressednotintheincreaseofthevoltageoftheresponsebutinthenumberofevokednerveimpulses.Healsoobservedtheadaptationofthesensoryorganstoprolongedstimuli. Sherringtonworkedonthereflexarcsofthespinalcordandinvestigatedthedistributionofthesegmentedskinfields.Discoveredthatnotjustmotorbutalsosensorynervefibersexistinthemuscles,andfoundtwosensoryapparatusinthemuscle:themusclespindleandtheGolgitendonorgan. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 67 SIR HENRY HALLETT DALE (1875-1968) OTTO LOEWI (1873-1961) DaleandLoewireceivedtheNobelPrizeinPhysiologyfordiscoveringtheneurotransmitteracetylcholineandtheirworkinthechemicaltransmissionofnerveimpulses. Dalesynthetizedacetylcholinefromergotandstudieditseffectsonlivingorganisms.Atthistimetwocontrarytheoriesexistedaboutthenatureofsignalingatthesynapse:onegroupofscientistsbelievedthatthesignalingwaschemical,andtheothersthoughtthatthetransmissionatthesynapsehasanelectricalnature.Dalesupportedthechemicalview.Lateritwasproventhatmostofthesynapsesarechemical,buttherearesomethatareelectrical. Daleoriginatedaschemeusedtodifferentiateneuronsaccordingtowhatneurotransmittertheyrelease.TheDale’sprinciplestatesthateachneuronreleasesonlyonetypeofneurotransmitter.Laterthisrulehasbeenshowntobefalse. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 68 SIR HENRY HALLETT DALE (1875-1968) OTTO LOEWI (1873-1961) Loewiidentifiedthefirstchemicalneurotransmitterinthenervoussystem.Thediscoveryofacetylcholinehappenedwiththehelponeofhisdreams: „ThenightbeforeEasterSundayofthatyear(1920)Iawoke,turnedonthelight,andjotteddownafewnotesonatinyslipofpaper.ThenIfellasleepagain.Itoccurredtomeat6o'clockinthemorningthatduringthenightIhadwrittendownsomethingmostimportant,butIwasunabletodecipherthescrawl.Thenextnight,at3o'clock,theideareturned.ItwasthedesignofanexperimenttodeterminewhetherornotthehypothesisofchemicaltransmissionthatIhaduttered17yearsagowascorrect.Igotupimmediately,wenttothelaboratory,andperformedasingleexperimentonafrog'sheartaccordingtothenocturnaldesign.„(Loewi,O.(1953).Fromtheworkshopofdiscoveries.Lawrence:Univ.OfKansasPress.) HenamedthesubstanceVagusstoffbecauseitoriginatedfromthevagusnerve. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 69 JOSEPH ERLANGER (1874-1965) HERBERT SPENCER GASSER (1888-1963) TheywontheNobelPrizeinPhysiologyin1944fortheirworkonthefunctionsofnervefibers. Erlangerbuiltthesphygmomanometerformeasuringtheimpulse-propagationoftheheart.HeworkedoutmodernanalysismethodsofneurosciencewiththehelpofGasser.ErlangerandGasserstudiednerveimpulseswiththehelpofcathoderaytubes.Theycouldrecordthetimecourseofnerveimpulsesforthefirsttime.Theyconfirmedthataxonsoflargediametertransmitnerveimpulsesmorequicklythanthinaxons.Theyclassifiedthenervefiberstothreegroupsaccordingtotheirproperties:A,B,C.Thethreegroupswerefurthersubdividedintosubgroups:Aalpha,Abeta,Agamma,Adelta.Cgroupalsohasgotsubdivisionscalleddorsalrootfiberandsympatheticfiber.ThefastestconductingfibersaretheAfibers. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 70 WALTER RUDOLF HESS (1881-1973) HessawardedtheNobelPrizeinPhysiologyorMedicinein1949formappingtheareasofthebraininvolvedinthecontrolofinternalorgans. Hessfirstcarriedoutchronicexperimentsoncatswhereelectrodeswereinsertedinthediencephalonoftheanimals.Duringhisstudiesofthehypothalamushefoundareasofthisbrainregionwhereelectricstimulationcausedanincreaseinthebloodpressure,riseofthefrequencyofheartbeatingandfasterrespiration.Stimulationonanothersitesdecreasedthebloodpressure,thepulserateandresultedinaslowerrespiration.Hecouldalsoevokeincreasedordecreasedurinating,defecationandbowelmovements.Stimulatingotherplacescouldinducesalivating,vomitingorachangeinthethermalregulation.Hecouldalsoelicitcomplexemotionalresponseslikerage.BylowfrequencystimulationofthethalamusheinducednaturallikesleepwithslowEEGactivity. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 71 GEORG VON BÉKÉSY (1899-1972) BékésyreceivedtheNobelPrizeinPhysiologyorMedicineforhisresearchonthefunctionofthecochleain1961. HeworkedatHungarianPostOfficeduringthetimeofhisdiscoveriesasanengineerandhadtosolveproblemsrelatedtolongdistancetelephonetransmission.Tomanagethetelecommunicationtasks,hewantedtounderstandthemechanismofhearing.SoBékésydevelopedamethodfordissectingtheinnerearofhumancadaversandstudiedthecochlea.Heobservedthatthebasilarmembranemoveslikeasurfacewavewhenstimulatedbysound.Differentfrequenciesofsoundcausedthemaximumamplitudesofthewavestooccuratdifferentplacesonthebasilarmembranealongthecoilofthecochlea.Hetheorizedthattheplacementofeachhaircellalongthecoilofthecochleacorrespondstoaspecificfrequencyofsound(tonotopy).Békésyalsodevelopedamechanicalmodelofthecochlealater. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 72 SIR JOHN ECCLES (1903-1997) ANDREW FIELDING HUXLEY (1917-) SIR ALAN LLOYD HODGKIN (1914-1998) TheywontheNobelPrizeinPhysiologyorMedicinefortheirworkonthesynapseandactionpotentialsin1963. Ecclesinvestigatedsynaptictransmissionusingthestretchreflexasamodel.Becausethisreflexconsistsonlyofasensoryandamotorneuron,itcouldbeeasilystudied.HeobservedEPSPs(excitatorypostsynapticpotential)orIPSPs(inhibitoryPSP)duringelectricalstimulationofparticularmuscles. HuxleyandHodgkininvestigatedthebehaviorofthecellmembraneonthegiantaxonsoftheAtlanticsquidwiththehelpofthevoltageclamptechnique.Theyhypothesizedtheexistenceofionchannelsandgaveanaccuratemathematicalmodeloftheactivationprocessesandpropagationoftheactionpotentials.(Hodgkin-Huxleymodel) ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 73 RAGNAR ARTHUR GRANIT (1900-1991) GEORGE WALD (1906-1997) HALDAN KEGGER HARTLINE (1903-1983) TheyreceivedtheNobelPrizeinPhysiologyfortheirstudiesontheneurophysiologicalandchemicalmechanismsofvisionin1967. Granitdevelopedamicroelectrodewhatheinsertedintheretinaofcatsandrecordedthefirstelectroretinogram.Hestudiedwhathappensintherodes,cones,ganglioncellsandnervefibers.Discoveredthetwotypesofreceptores(rodsandcones)andthethreeconessensitivetodifferentcolorsofthelight.SotheYoung-Helmholtztheoryoftrichromaticcolorvisionwasfinallyproven. WalddiscoveredtherelationshipbetweenvitaminAandthephotopigmentrhodopsinandshowedthatvitaminAwasessentialinretinalfunction. Hartlinerecordedtheelectricalactivityfromtheretinacrabsandfrogsanddiscoveredthereceptivefieldsintheeyeandthatareasnexttoactivatedphotoreceptoresareinhibited. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 74 SIR BERNARD KATZ (1911-2003) JULIUS AXELROD (1912-2004) ULF SVANTE VON EULER (1905-1983) TheNobelPrizewasawardedtothemin1970fortheirworkonneurotransmitters,chemicaltransmissionandthemechanismsrelatedtothem. Katzstudiedthebiochemistryandactionofacetylcholine,andfoundthatthereisalwaysadefinednumberofneurotransmittersinthevesiclesattheneuromuscularterminal.Fromthesevesiclesaquantumofneurotransmittersarereleasedtothesynapticcleftduringtheexocytosisaftertheinfluxofcalciumions. Axelrod’smajorworkwasontherelease,reuptake,andstorageoftheneurotransmittersepinephrineandnorepinephrine.Laterhecarriedoutresearchesonthepinealgland. EulerdiscoveredthesubstancePandthenoradrenalin(norepinephrine).SubstancePisapeptidthatisfoundinthebrainandspinalcord,andisassociatedwithinflammatoryprocessesandpain. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 75 DAVID HUNTER HUBEL (1926-) and TORSTEN NILS WIESEL (1924-) ROGER WOLCOTT SPERRY (1913-1994) Theyreceivedin1981theNobelPrizeinPhysiologyorMedicinefortheirresearchesrelatedtotheinformationprocessinginthevisualsystem. HubelandWieselinsertedmicroelectrodesintotheprimaryvisualcortexofanesthetizedcatsandcategorizedtheresponsiveneurons.Theyalsodiscoveredtheoculardominancecolumnsinthevisualcortexandmadeimportantstudiesrelatedtocorticalplasticity. Sperrymaderesearchesonpatientswithuntreatableepilepsy,whounderwentcallosotomy,wherethecorpuscallosumwascutthroughtoseparatethetwohemispheresofthebrain.Hemadeinterestingexperimentstoexaminethedifferencesbetweentherightandlefthemisphere.Hisstudiescontributedgreatlytounderstandingthelateralizationofbrainfunctions. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 76 ERWIN NEHER (1944-) BERTSAKMANN (1942-) TheywereawardedtheNobelPrizeinPhysiologyorMedicinein1991forthedevelopmentofthepatch-clamptechniqueandfortheirstudiesonthefunctionandbehaviorofsingleionchannelsinthecellmembrane. Withthehelpofamicropipettetheycouldisolateatinyareaofthecellmembraneindifferentways(Cell-attachedpatch,wholepatch,inside-outpatch,outside-outpatch)andrecordthemoleculareventsofionchannelslocatedhereandtomeasurethetransmembranecurrent.Shortlyafterinventingthepatch-clamptechnique,researchesonthestructureoftheionchannelsincreasedtounderstandtheirfunction. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 77 ARVID CARLSSON (1923-) ERIC KANDEL (1929-) PAUL GREENGARD (1925-) TheyreceivedtheNobelPrizeinPhysiologyorMedicinein2000. CarlssonstudiedtheneurotransmitterdopamineanditseffectsinParkinson'sdisease.Hedevelopedamethodformeasuringtheamountofdopamineinbraintissuesandshovedthatdopaminelevelsinthebasalgangliaarehigh.Basalgangliaisabrainareaimportantformovementorganization.HecouldreducethesymptomsofParkinson’sdiseasewithL-dopa,whichistheprecursorofdopamine. Kandeldidresearchonthephysiologicalbasisofmemorystorageinneurons.HeusedasimpleanimalmodeltheAplysiacalifornica(Californiaseahare). Greengard’sexperimentsfocusedoneventsinsidetheneuroncausedbyneurotransmitters:hestudiedthebehaviorofsecondmessengercascadesthattransformthedockingofaneurotransmitterwithareceptorintopermanentchangesintheneuron. ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 78 REFERENCES Finger, S.: Originsof Neuroscience, A Historyof ExplorationsintoBrainFunction, Oxford Univ. Press, New York, 1994. Ochs, S.: A Historyof NerveFunctions, FromAnimalSpiritstoMolecularMechanisms, Cambridge Univ. Press, 2004. Goldensohn, E.S.: Animal electricity from Bologna to Boston. Electroenceph. clin. Neurophysiol. 1998, 106: 94-100. Piccolino,M.: Animal electricity and the birth of electrophysiology: The legacy of Luigi Galvani, Brain Re. Bull. 1998, 46:381-407. Brazier, MAB, The historical development of neurophysiology. In Handbook of PhysiologyVol.1.Field,J., H.W Magoun, VEHall, Eds. American Physiological Society, Washington, DC, 1-59. http://nobelprize.org/nobel_prizes/medicine/nerve_signaling.html http://www.ibro.info/Pub/Pub_Main_Display.asp?LC_Docs_ID=3085#sub http://faculty.washington.edu/chudler/nobel.html ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 79 REVIEW QUESTIONS What was the electroscope used for? How stored the leydenjar the electric charges? Which theory wanted Swammerdam to prove with his experiments? What was the point of his experiments? What was Galvani’s „animal electricity”? What was the structure of the first battery, the voltaic pile? Who stimulated first the human brain electrically? Name some early electrical measurmentdevices! Who measured the nerve conduction velocity first? What was his experimental set-up? What was the Horsley-Clarke apparatus used for? Who invented a the electroencephalogram? What was the first brain rhythm he discovered? ELECTROPHYSIOLOGICAL METHODS OF THE STUDY OF THE NERVOUS-AND MUSCULAR SYSTEMHISTORY OF ELECTROPHYSIOLOGY