碩士 / 國立清華大學 / 生命科學系 / 89 / At the start of the 20th century, scientists have hypothesized that learning and memory could be encoded in the strength of the synaptic connections between neu- rons（Tanzi, E., 1893）. In 1970s, scientists reported that high-frequency stimulation input to the dentate gyrus produced a long-lasting enhancement of field potential (Bliss and Lomo, 1973), they called long-term potentiation(LTP). Most of the LTP phenomens are related to the glutamate receptors. NMDA receptor is one of the glutamate receptors, it is not only the ligand-gated ion channel but also the voltage dependent receptor (Watkins and Krogsgaaard-Larsen, 1990). At the usual resting membrane potential, the ionic channels are normally blocked by magnesium ions (Mg2+ ). The magnesium will be removed when the postsynaptic neuron depolarization reaches the threshold, and the ionic channels will be opened. After the ionic channels opening， the calcium will influx and induce the LTP (Zador and Koch, 1990; Holmes and Levy, 1990). In 1940s，Donald Hebb advanced an idea regarding the conditions that cause synapses change (Hebb, D.O., 1949), and that might be interpreted the LTP induced by the NMDA receptors. The Hebb's hypothesis should be based on coincidence detection, that is strengthening of the synapse only occur when the release of neurotransmitter from a presynaptic terminal coincides with the depolarization of the postsynaptic cell (Kelso and Ganong, 1986). For the NMDA receptors, when the stimulation inputs are combined with the postsynaptic depolarization, the magnism will be removed that cause calcium influx and induce LTP (Brown and Ganong, 1990; Bliss and Collingridge, 1993). Therefore, the NMDA receptor is a coincidence detector, it might fit the Hebb's hypothesis.
Voltage-sensitive gap junction is a special kind of gap junction, the channels between the cells will be opened only when the postsynaptic cell is more depolarization than the presynaptic cell (Gianume and Kado, 1987; Jaslove and Brink, 1986). Coincidence detection occurs when presynaptic cells are linked to a postsynaptic cell through voltage-sensitive gap junction (Edwards and Shih-Rung, 1998; Edwards and krasne, 1999). When spikes in two presynaptic neurons are synchronous, they act as one large input and produce a large EPSP. When two inputs are asynchronous, the depolarization created by the early input blocks entry of the late synaptic currents (Heitler and Edwards, 1998). Both voltage-sensitive gap junction and NMDA receptor are the coincidence detectors. Therefore, we expect that the voltage-sensitve gap junction can induce LTP. In this report, we shocks the primary afferent neurons of the crayfish escape circuit and records the exicited postsynaptic potentials（EPSPs）in lateral giant（LG） neuron. We find that tetanic stimulatioms can induce LTP. There are two synapse types between the afferent neurons and postsynaptic neuron (wine and Krasne, 1982). They are cholinergic synapses and voltage-sensitve gap junction, so we block the cholinergic synapses with it's inhibitors and find that enhancement phenomen did not disappear suggesting that the LTP phenomen do not come from the cholinergic synapses, and it shall be came frome the voltage-sensitve gap junction.
The calcium and calcium-dependent enzymes are very important in LTP mechanisms (Johnston and Williams, 1992; Bliss and Collingridge, 1993; Nicoll and Malenka, 1995), we exam whether the calcium and calcium-dependent enzymes play important roles in voltage-sensitive gap junction induced LTP. We inject the calcium chelators and carry out the tetanic stimulations (Magali and Ruth, 1999), and find that the EPSPs increased phenomens have been inhibited. It suggests that the calcium play a role in the LTP that induced by voltage-sensitive gap junction. When the [Ca2+ ] iare increased, it can activate the calcium- dependent enzymes (ex: PKA, PKC, CaMII ) (Alberini and Ghirardi, 1995; Huang and Nguyen, 1996). And these enzymes induce the second messanger reactions that influence the gene expression. Some postsynaptic cells will be released the second messangers (ex: NO, O'Dell and Huang, 1994) and diffuse to the presynaptic cells. These reactions result in the characteristic changes of the presynaptic cell and postsynaptic cell, and the responses of the same stimulation will change. We inject the PKA inhibitors into the LG or inflow the buffer with the PKC inhibitor and carry out the tetanic stimulation (Karunesh and Lazlo, 2000). We find that the EPSPs increased phenomens still exist when inject the PKA inhibitors, and the increasement phenomens have be inhibited when the PKC inhibitors exist. It suggests that the PKC may play an important role in the LTP induced by voltage-sensitive gap junction, but the PKA may not play a role in LTP induced by voltage-sensitive gap junction.
| Identifer | oai:union.ndltd.org:TW/089NTHU0105071 |
| Date | January 2001 |
| Creators | Wen-Bin Kao, 高文彬 |
| Contributors | Shih-Run Yeh, 葉世榮 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 34 |
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