1 8 2 Vertebrate Learning and Memory BIO 361T Fall 2014 1 Why is LTP inhibited in mice that are injected with an NMDA R antagonist Explain the molecular mechanism that is normally operating and at what point it is being interrupted If the NMDA R is blocked Ca2 in the CA1 cannot be increased by high intensity stimulation This would normally occur when more Glu is released by the CA3 neuron causing an EPSP via the AMPA R which displaces Mg2 from the NMDA R allowing Ca2 to enter This increases AMPA insertion at the membrane AMPA sensitivity to Glu and Glu release by CA3 An antagonist would prevent CA1 from increasing its response to repetitive high intensity stimulation of CA3 resulting in no cellular memory 2 Predict the molecular and phenotypic effects on LTP of injecting CA1 neurons with chemicals that chelate bind up decreasing intracellular concentrations of Ca2 If Ca2 could not act as a second messenger in the CA1 neuron it would not activate CaMKII or PKC which are responsible for increasing CA1 responsivity to CA3 LTP would fail to be induced 3 Mice are especially good models for studying the cellular and molecular basis of many processes because their genome is sequenced and many mutants are commercially available One such mutant is the CaMKII knock out KO mouse in which both copies of the gene that encodes CaMKII have been removed What would you expect the phenotype of a CaMKII KO mouse to be What other genes could you knock out to elicit a similar phenotype No LTP induction Could knock out AMPA R or NMDA R among others 4 Explain the statement that CA1 neurons affect CA3 neurons in a retrograde moving backwards fashion CA1 neurons must release some factor that goes to the pre synaptic neuron CA3 to increase Glu release Candidate molecule is nitric oxide which is a gaseous neurotransmitter and can diffuse quickly 2 5 The rabbit has been useful for studies on classical conditioning employing the eye blink reflex which is controlled by neurons in the cerebellum Use what you learned in your homework and the following figure to define the abbreviations UR CR CS and US and explain how they are related in this paradigm of classical conditioning UR unconditioned response blinking due to a puff of air to the eye CR conditioned response blinking due to a sound tone being played after several rounds of playing a tone before the puff of air CS conditioned stimulus the sound tone which becomes associated with the air puff due to timing of stimuli presentation US unconditioned stimulus the eye puff which naturally elicits the unconditioned response or eye blink 6 Newborn chicks and ducklings imprint onto the visual cue of their mother and learn to follow her This early form of learning has been studied by providing neurons with radioactively labeled uracil molecules and measuring its incorporation into cells while imprinting chicks onto artificial objects in the laboratory Why would neurons use this molecule How would it allow you to differentiate between short term and long term memory Uracil is used to make RNA so it will be necessary during transcription Only long term memory involves synthesis of new molecules like RNA and protein Short term memory should not induce differential uptake or incorporation of radioactive uracil because it does not induce protein synthesis 7 Incorporation of 3H uracil was found to be highest in neurons of the roof of the front of the brain forebrain providing a candidate brain area for further study in learning and memory Lesioning this area before training prevented imprinting Lesioning this area after training destroyed the preference for the artificially imprinted on object What would you conclude from these experiments How does this area differ from the hippocampus in mammals The forebrain roof is involved in both formation and storage of imprinting memories The hippocampus and mechanism of LTP appear to be involved in formation but not storage as LTP decays after 1 2 weeks long before memory decays 8 Research in mammals and birds suggests that auditory memory involves brain regions associated with the auditory system instead of the hippocampus In many songbird species males learn their conspecific song from an adult tutor male They memorize their species specific song as juveniles and sing it when they sexually mature They listen to their own singing compare it to their memorized song to refine their song as they become adults Electrophysiological recordings of the songbird brain show that while singing several clusters of neurons are highly active that are part of the song system in the brain Do you think this is evidence that song memorization occurs in these neurons Why or why not The song system nuclei appear to be involved in listening to song but not producing it remembering it or committing it to memory 3 9 What would you do to further investigate which neurons are responsible for song memorization What are some candidate brain areas the places you would look first What are some potentially confounding variables Record while bird listens to tutor conspecific vs heterospecific songs pre vs post training Look in auditory associated areas Neurons in the High Vocal Center HVC of the cerebrum respond more strongly to conspecific than heterospecific song Early in maturity they are more responsive to the tutor s song then they shift preference to the adult bird s own song so they are not merely song activated Further the volume of the cell bodies of these neurons increased during memorization phase indicative of active gene expression and protein synthesis but not when the bird matured and began singing see Bolhuis and Gahr s Nature Neuroscience review 2006
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