碩士 / 國立成功大學 / 藥理學研究所 / 89 / Long-term potentiation (LTP) is characterized by its rapid induction and remarkable stability. In the past few years, most studies investigated the mechanism for its rapid induction. However, it is still unclear about the mechanisms underlying the conversion of initial potentiation into a persistent state. The consolidation of LTP plays a crucial role in memory formation, so it will help us to understand the mechanism of learning and memory. Therefore, the principle purpose of this study is to explore what factors and mechanisms contribute mechanism of the mossy fiber — CA3 LTP consolidation. The strategy of this study is to explore the causes of LTP reversal(depotentiation).
Using mouse hippocampal slices, we have studied the induction of depotentiation of long-term potentiation (LTP) at the mossy fiber synapses onto CA3 pyramidal neurons. A long train of low-frequency (1 Hz/900 pulses) stimulation (LFS) induced a long-term depression of baseline synaptic transmission or depotentiation of previously established LTP, which was reversal and was independent of NMDA receptor activation. This LFS-induced depotentiation was observed when the stimulus was delivered 1 or 10 min after LTP induction. However, when LFS was applicated at 30 min after induction, significantly less depotentiation was found. The induction of depotentiation on one input was associated with a heterosynaptic reverse of the LTP previously induced on a separate pathway. In addition, this LFS-induced depotentiation appeared to be mediated by the activation of group 2 metabotropic glutamate receptors (mGluRs), because it was mimicked by bath-applied group 2 agonist (2S, 2’R, 3’R)-2-(2’, 3’-dicarboxycyclopropyl) glycine (DCG-IV) and was specifically inhibited by the group 2 antagonists, (S)-a-methyl-4-carboxyphenylglycine (MCPG) and (aS)-a-amino-a-(1S,2S)-2-carboxycyclopropyl-9H-xanthine-9-propanic acid (LY341495). Moreover, the induction of depotentiation was entirely normal when synaptic transmission was blocked by glutamate receptor antagonist kynurenic acid and was associated with a reversal of PPF attenuation during LTP expression. Pretreatment of the hippocampal slices with Gi/o protein inhibitor pertussis toxin (PTX) prevented the LFS-induced depotentiation.
Additionally, the expression of mossy fiber LTP was not affected by removing of extracellular Ca2+ after LTP induction, suggesting that mossy fiber LTP dose not need persistent Ca2+ influx. Furthemore, we also found that dynorphin can mimic LFS to induce time dependent depotentiation. However, the opioid receptor antagonist naloxone, has no effect on LFS-induced depotentiation. These results suggest that LFS-induced depotentiation is primarly caused by glutamat-mediated cascade. Because protein phosphatase 2B inhibitor can also inhibit LFS-induced depotentiation, we predict that protein phosphatase 2B (PP2B) may also involve in LFS-induced depotentiation.
In Westorn blotting experiments, we found that HFS-induced LTP is associated with an increase of rabphilin phosphorylation, and LFS significant reverses this effect. However, HFS-induced LTP did not cause significant any changes the phosphorylated state of Rim. Taken these results togrther, we proposed that activation of presynaptic group 2 mGluR and in turn triggering a PTX-sensitive Gi/o-protein-coupled signaling cascade and dephosphorylation of rabphilin may contribute to the LFS-induced depotentiation at the mossy fiber-CA3 synapses. However, the change of the phosphorylation state of Rim protein dose not involved on the LFS-induced LTP or LFS-induced depotentiation at mossy fiber-CA3 synapses.
| Identifer | oai:union.ndltd.org:TW/089NCKU0550010 |
| Date | January 2001 |
| Creators | Yea-lin Chen, 陳雅琳 |
| Contributors | Kuei-Sen Hsu, 許桂森 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 0 |
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