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Storage of Spatial Information by the Maintenance Mechanism of LTP

Storage of Spatial Information by the Maintenance Mechanism of LTP. Pastalkova et al. Science 313:1141-1144, 2006. Background. There are two (three?) phases of LTP: Short, intermediate, and long Late-term LTP is dependent on gene transcription and protein synthesis. Background.

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Storage of Spatial Information by the Maintenance Mechanism of LTP

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  1. Storage of Spatial Information by the Maintenance Mechanism of LTP Pastalkova et al. Science 313:1141-1144, 2006.

  2. Background • There are two (three?) phases of LTP: • Short, intermediate, and long • Late-term LTP is dependent on gene transcription and protein synthesis

  3. Background • PKMz is a constituatively active form of PKCz • z= zeta • PKMz does not require calcium or diacylglycerol activation • PKMz is transcribed independently of PKCz and maintains the late LTP • A synthetic peptide, z-pseudosubstrate inhibitory peptide (ZIP) mimics the regulatory domain of PKCz

  4. Hypotheses • Can PKMzetainhibiton by ZIP reverse the late phase of LTP in vivo? • Does ZIP cause retrograde loss of spatial memory?

  5. Figure 1

  6. Figure 1

  7. Figure 1

  8. Figure S1, S2

  9. Figure 1 3D rendering of PKMzeta

  10. Conclusion PKMzinhibiton reverses the maintenance of late-phase LTP in vivo

  11. Figure 2

  12. Figure 2 http://www.nimh.nih.gov/science-news/2007/memory-sustaining-enzyme-may-help-treat-ptsd-cognitive-decline.shtml

  13. Figure 2

  14. Figure S3

  15. Conclusion PKMz inhibition abolishes long-term retention of spatial information

  16. Figure 3

  17. Figure 3

  18. Figure S4

  19. Figure S5

  20. Conclusion Inhibition of PKMz, but not other protein kinases, disrupts memory storage

  21. Conclusions • PKMz inhibition specifically disrupted the long-term retention and not LTP encoding or short-term memory • Inhibition of PKMz affects information storage as opposed to retrieval • These effects are specifically due to PKMz inhibition and not inhibition of CaMKII, PKA, or c/nPKCs

  22. Summary diagram

  23. Epilogue Rapid Erasure of Long-Term Memory Associations in the Cortex by an Inhibitor of PKMz Shema et al. Science 317:951-953, 2007

  24. Brief Overview • Conditioned taste aversion, saccharin = CS • Infused ZIP bilaterally into the insular cortex (where gustatory memory is stored) • ZIP in the IC blocked expression of conditioned taste aversion 1 week and 1 month after infusion

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