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

Figure 1

3D rendering of PKMzeta

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

Figure 3

Figure 3

Figure S4

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