Storage of Spatial Information by the Maintenance Mechanism of LTP
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Transcript of 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
• 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
Hypotheses
• Can PKMzeta inhibiton by ZIP reverse the late phase of LTP in vivo?
•Does ZIP cause retrograde loss of spatial memory?
Figure 1
Figure 1
Figure 1
Figure S1, S2
Conclusion
PKMz inhibiton reverses the maintenance of late-phase LTP in vivo
Figure 2
http://www.nimh.nih.gov/science-news/2007/memory-sustaining-enzyme-may-help-treat-ptsd-cognitive-decline.shtml
Figure 2
Figure 2
Figure S3
Conclusion
PKMz inhibition abolishes long-term retention of spatial information
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Figure 3
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Figure S5
Conclusion
Inhibition of PKMz, but not other protein kinases, disrupts memory storage
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
Summary diagram
Epilogue
Rapid Erasure of Long-Term Memory Associations in the Cortex by an Inhibitor of PKMz
Shema et al. Science 317:951-953, 2007
• 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
Brief Overview