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Complexities of Long-Term Potentiation

Complexities of Long-Term Potentiation. From Mechanisms of Memory by J. David Sweatt, Ph.D. Potential Sites of Synaptic Modification in LTP. Retrograde Signal. Release. Membrane Properties. Glu. Binding. Reuptake. Postsynaptic = Altered Number of AMPA receptors

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Complexities of Long-Term Potentiation

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  1. Complexities of Long-Term Potentiation From Mechanisms of Memory by J. David Sweatt, Ph.D.

  2. Potential Sites of Synaptic Modification in LTP Retrograde Signal Release Membrane Properties Glu Binding Reuptake • Postsynaptic= Altered • Number of AMPA receptors • Insertion of AMPA receptors • Ion flow through AMPA channels • Membrane electrical properties • Presynaptic= Altered • Neurotransmitter amount in vesicles • Number of vesicles released • Kinetics of release • Glutamate reuptake • Probability of vesicle fusion Additional possibilities include changes in number of total synaptic connections between two cells

  3. E-S Potentiation in area CA1 B A Data courtesy of Erik Roberson

  4. GABA-ergic interneuron model of E-S Potentiation CA1 Axon GABAergic Neuron - GABA Cl- Diminished Cl- channel function produces increased excitability + Schaffer Collaterals

  5. Temporal integration in LTP induction Threshold for triggering an action potential High Frequency Stimulation Membrane potential (mV) -70 Low Frequency Stimulation Time

  6. Theta Frequency Stimulation A C 5-Hz … 200 msec 200 msec 200 msec 200 msec 200 msec • 5-Hz frequency for 30 sec • 150 total pulses 200 175 150 fEPSP slope (% of baseline) 125 100 75 -20 0 20 40 60 D Time (min) 5 4 B Dual Recording 3 2 Stratum Pyramidale 1 0 Stratum Radiatum 0 10 20 30 Time during TFS (sec) 2 mV 5 msec Theta Frequency Stimulation Population Spike Amplitude: EPSP slope (Normalized) Data and figure courtesy of Joel Selcher

  7. GABA-b receptors in temporal integration with TBS CA1 Axon GABAergic Neuron - GABA - GABA-b receptor Negative feedback onto presynaptic GABA-b receptors causes decrease in GABA release + Schaffer Collaterals

  8. Immediate, Early and Late LTP 250 200 150 100 50 -30 0 30 60 90 120 150 180 EPSPSlope (Percent of Baseline) 250 200 150 100 50 -30 0 30 60 90 120 150 180 Time (minutes) Roberson, English and Sweatt (1996) Learn. Mem. 3:1-24

  9. Induction, Maintenance and Expression of LTP EXPRESSION BLOCKED EPSP MAINTENANCE BLOCKED INDUCTION BLOCKED PERIOD OF DRUG TREATMENT time tetanus

  10. Mechanisms of Induction, Maintenance and Expression Induction I-LTP maintenance Expression Induction Expression E-LTP maintenance Induction Expression L-LTP maintenance

  11. Dendrites with Spines A B mCD8 Distal Courtesy of Liqun Lou, Stanford University Courtesy of E. Korkotian, The Weismann Institute

  12. Injection of PKC inhibitor PKC inhibitor Cell Body

  13. Candidate Retrograde Signaling Molecules Physical Coupling (i.e. Integrins) Signal Signal Diffusible Messengers (i.e. NO, O2-, AA)

  14. Silent Synapses Back propagating Action Potential Depolarization Silent Synapse NMDA Receptor AMPA Receptor Vesicle

  15. Alternative Mechanisms for LTP Renger, Egles, and Liu (2001) Neuron 29:469-484.

  16. Depotentiation and LTD A B C Lee et al. (2000) Nature 405:955-959.

  17. Modulation of LTP induction A B C Thomas, Moody, Makhinson and O’Dell (1996) Neuron 17:475-482. Gottschalk, Pozzp-Miller and Figurov (1998) J. Neurosci. 18:6830-6839 Johnston, Hoffman, Colbert, and Magee (1999) Curr. Opin. Neurobiol. 9:288-292.

  18. LTP Outside the Hippocampus Shafe et al. J. Neurosci. 20:8177-8187.

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