碩士 / 國立陽明大學 / 生理學研究所 / 91 / Abstract
Long-term potentiation (LTP) and depression (LTD) are persistent increase and decrease respectively in synaptic efficacy, depending on previous history of synaptic activity in the CNS. At hippocampal CA1 synapses, two distinct forms of LTD have been described, namely the NMDA receptor-dependent LTD that can be induced by stimulation consisting of 900 pulses at 1 Hz, and the metabotropic glutamate receptor—dependent LTD, induced by paired-pulses (interval = 50 ms) stimulation consisting of 900 pairs delivered at 1 Hz. In a pervious study, we reported that LTD could be induced at CA1 synapses by delivering 100 pulses of paired-pulses with interval of 10 ms to Schaffer collateral branches every 6 secs. In this study, we wish to find out whether LTD induced by this new stimulation protocol is NMDA-R dependent or mGluR-dependent, and also to address the relative characters and physiological significance of the present LTD.
We first confirmed that the 10ms-paired-pulse (10 ms-pp) stimulation protocol could, while stimulation with single pulse could not, induce LTD (67 ± 4 %) at CA1 synapses, results that are consistent with our previous finding. The induction of LTD by 10 ms PP was occluded following the induction of saturated mGluR-dependent LTD induced by bath application of DHPG (DHPG-LTD). In addition the induction of PP-LTD was Protein kinase C-independent, a feature that is similar to DHPG-LTD. Most importantly, LTD induced by 10 ms-pp was completed blocked upon application of MPEP (6-methyl-2-(phenylethynyl)-pyridine), an antagonist of mGluR5 receptor. On the other hand, it was unaffected by AP-5 (2-amino-5-phosphonovalerate), a antagonist of NMDA-R. Taken together, the above results suggested that LTD induced by 10 ms-pp was analog to DHPG-LTD.
Increasing the pulse number from 2 to 3, 4, or 6 pulses resulted in the different alternations of synaptic efficacy: 3 pulses protocol resulted in no significant change in synaptic efficacy (112 ± 10 %), while LTPs were induced by 4-pulses (155 ± 17 %) and 6-pulses (156 ± 9 %) protocols. Upon the blockage of mGluR5 receptors, 3-pulses protocol induced significant LTP (141 ± 7%); however, LTPs induced by 4-pulses and 6-pulses protocols were unaffected. Taken together, we have demonstrated a pulse-number-dependent bidirectional plasticity at CA1 synapse, and the factors regulating the sign of synaptic efficacy were the profile of the activation of different subtypes of glutamate receptor by different stimulating protocols and the interaction between the downstream molecules. Accordingly, we purpose that in the experimental condition under which the functions of NMDA receptors was blocked but is remained for group I mGluR, the 4- and 6-pulses protocol should induce LTD. This prediction was however not observed as the 4- and 6-pulses protocols actually resulted in only inhibition of LTP, but not in LTD induction. Nevertheless, LTDs were induced by 4- and 6-pulses protocols in a condition that functions of both PKC and NMDA-R were completely blocked, suggesting that desensitization of group I mGluR mediated by PKC was turned on during 4- and 6-pulses protocols, which in turn inhibited induction of LTD.
In conclusion, we have reported in this study a new electrical stimulation protocol that can induce LTD analog to DHPG-LTD. This electrical stimulation protocol consists of delivering 100 paired-pulses at every 6 seconds with the interval between the paired-pulses being 10 ms. Increasing pulse number could activate NMDA-R dependent LTP. This observation suggested that, at CA1 synapses, the synaptic efficacy could undergo bi-directional change and the sign of synaptic change is not only dependent on the frequency of electrical stimulation as previously reported but also on the number of pulses delivered, i.e. PNDP. The sign of PNDP was determined by profile of activation of NMDA-R mGluR and PKC.
| Identifer | oai:union.ndltd.org:TW/091YM000116012 |
| Date | January 2003 |
| Creators | Jui-Cheng Hsu, 許瑞城 |
| Contributors | Tsai-Hsien Chiu, Ming-Yuan Min, Hsiu-Wen Yang, 邱蔡賢, 閔明源, 楊琇雯 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 90 |
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