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Wie Nervenzellen Gedächtnisspuren ablegen -Lernen aus neurobiologischer SichtBjörn BrembsFreie Universität Berlinhttp://brembs.net
Wer wir sindGelernt oder geerbt?
Gerlernt - geerbtkeinsinnvollerKontrastFutter- ÜbelkeitVERMEIDUNG DES FUTTERSTon- SchockSCHRECKREAKTION BEI TONGABETon- ÜbelkeitKEIN EFFEKTFutter- SchockKEIN EFFEKTGarcia Effekt
Drei Faktoren steuern Verhalten
Adenylatzyklase (rutabaga-Gen)Ligand(Rutabaga)G-Protein
URPavlov‘s HundStimulus SubstitutionKlassisches Konditionieren
Klassisches KonditionierenWichtig!CS: conditionedstimulus (Glocke)
US: unconditionedstimulus (Futter)
UR: unconditionedresponse (Speicheln)
CR: conditionedresponse (Speicheln)Aktionspotential (Ca2+)AxonPräsynapseVesikel mitTransmitterPostsynapseRezeptormoleküleSynaptische Plastizität
Die Meeresschnecke AplysiaDie Fruchtfliege DrosophilaDie HonigbieneDreiModellorganismenzumStudiumderzellulärenVorgängenbeimLernen und derGedächtnisbildungWas machen Neuronen beim Lernen?
Eric Kandel: Aplysia
Aplysia californica(See-Hase)
USpaURCS-USKonvergenzpunkt!CSURKlassisches Konditionieren
Vorgänge am CS-US KonvergenzpunktBahnung von sensori-motorischen SynapsenVorher:Nachher:USURCSPrä-SynapseAP Verbreiterung:Prä-synaptischer MechanismusPost-SynapseSN: Sensorisches NeuronMN: Motor-NeuronIN: Interneuron
Adenylatzyklase (rutabaga-Gen)Ligand(Rutabaga)G-Protein
Molekulares LernenURUSStarke ReaktionCSURUSAP-VerbreiterungKonvergenz von CS und US am molekularen KoinzidenzdetektorCS
Bailey C. et.al. PNAS 1996;93:13445-13452©1996 by The National Academy of Sciences of the USALangzeit-GedächtnisKiemenrückzugTage nach dem Training
Klassisches KonditionierenOlfaktorisches Lernen in DrosophilaFurchtlernen in Ratten und MäusenLidschlussreflex in KaninchenPER Konditionierung bei Bienenu.v.m.Mittlerweile sind die molekularen, neuronalen und Netzwerk-Mechanismen des klassischen Konditionierens sehr weit erforscht.Diese Mechanismen scheinen in allen Tierarten von der Schnecke bis zum Menschen prinzipiell sehr ähnlich abzulaufen (evolutionär konserviert)
Patient H.M. (1926-2009)1953:Medianer Schläfenlappen
 Schwere anterograde Amnesie
 Partielle retrograde Amnesie
 Intaktes Arbeits-GedächtnisHenry Molaison, 1970sMotorisches Lernen des Patienten HMSelektive Störung desdeklarativen GedächtnissesH.M. zeigtnormalesmotorischesLernen (operant!)Patient H.M. (1926-2009)
Memento
Deklaratives Lernen: Hippocampus
Hippocampus-Scheiben im LaborAbleitelektrodeReizelektrode(Ratte!)
Hippocampus: LTP
---+++---+++CytoplasmaSynaptischerSpaltCytoplasmaSynaptischerSpalt Ca++GlyGly Ca++ Mg++ Ca++ Mg++Glu++++----++++----GluGlutamatplusDepolarisationGlutamatalleineNMDA-Rezeptoren (Glutamat)
LTP: Postsynaptische MechanismenVorherTrainingNachherwenig WeiterleitungWeiterleitungWeiterleitung
LTP Variationen„assoziatives“ LTP
Kurzzeit-Gedächtnis:Verstellung der synaptischen Über-tragung mit den vorhandenenStrukturen undMolekülen: Dendriten, Axone, SynapsenLangzeit-Gedächtnis:Spezifische Aktivierung von Genen, Neubildung von Strukturen: ZellkernÜbergang Kurz- zu Langzeitgedächtnis
LTP: Strukturelle Veränderungen
Das lineare Modell der GedächtnisbildungFunktioniert unser Gehirn tatsächlich wie eine Festplatte?Gedächtnis-Konsolidierung
Drosophila im stationären Flug
Verhaltenskonsequenzenoperantklassisch
Adenylatzyklase (rutabaga-Gen)Ligand(Rutabaga)G-Protein
Ein neuartiger Lernmechanismusrut-AC (Synaptische Plastizität)Protein Kinase CNotwendigNicht notwendigklassischNotwendigNicht notwendigoperant
Mehrere LernsystemeReicht synaptische Plastizität nicht aus?

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Lernen aus Neurobiologischer Sicht