A Role of Protein Kinase in Fear Memory Formation
| Autor: | Pei-hsuan Shen, 沈佩萱 |
|---|---|
| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 People who have faced natural disasters or serious crime may get Post Traumatic Stress Disorder(PTSD), and develop not only physiological but also psychological trauma. However, if we know better about the formation, maintanance and storage of fear memory, we may help PTSD patient overcome the event. There are many signal cassade involved in memory formation, and protein kinase M zeta is one of them. PKM zeta is constitutively active, and catalytic fragment of PKC zeta. It’s an atypical form of protein kinase C, and has been proven to be important in maintenance of hippocampus-dependent memories and long-term potentiation. The purpose of this study is to investigate the involvement of PKM zeta in fear memory formation and the underlying mechanism of PKM zeta action. First, we used a myristoylated ζ -pseudosubstrate inhibitory peptide (ZIP) to selectively inhibit PKM zeta. After fear-conditioning(CS-US) training, ZIP was injected bilaterally into the amygdala, and then fear response was analyzed. We found that fear response in ZIP-injection group was lower than that in CS-US group. Second, we used another behavior protocol to investigate if ZIP-treated rats showed spontaneous recovery or reinstatement after ZIP injection. The results showed none of these happened, which meant that PKM zeta was important for fear memory maintenance, and showed no spontaneous recovery or reinstatement. Finally, we want to know how PKM zeta is involved in fear memory by using biotinylation and immunoprecipitation to detect the change of surface GluR1/GluR2 and internal GluR1/GluR2 after ZIP injection. Western blot data showed that surface GluR1/GluR2 were lower in ZIP-injection group than in CS-US group, and internal GluR1/GluR2 were both higher in ZIP-injection group. Blockade of PKM zeta impaired fear memory, caused reduction of surface GluR1/GluR2 and increased internal GluR1/GluR2. Therefore we conclude that PKM zeta plays an important role in fear memory maintenance, and it may inference fear memory and LTP through the regulation of GluR1/GluR2 receptor trafficking. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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