| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
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| Research Abstract |
Mammalian brain memory is hypothesized to be established through two phases; short-term plasticity, as exemplified by long-term potentiation (LTP) where pre-existing synapses change transmission efficiency, and long-lasting plasticity where new synapses are formed. Linkage between these phases, however, has not been verified experimentally due mainly to the lack of good model system for analysis. Recently several reports have described morphological changes at synaptic sites after a tetanic stimulation, claiming that these changes should be the verification of long-term memory. However, it is not proven that those morphological changes would be maintained for a truly long period.
In the present research, using the cultured slice of the rat hippocampus as the ex vivo system for the investigation of truly 'long-term' synaptogenesis, I pursued long-term effects following the induction of late-phase LTP. I found that the repetitive induction of late-phase LTP by brief applications of forsko
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lin led to long-term synaptogenesis as judged from electrophysiological, cytological and ultrastructural indices. The single application of forskolin produced LTP but not long-lasting synaptogenesis. Those indices include; 1) field postsynaptic potential standardized by field action potential, which should represent the number of synapses per neuron; 2) the amounts of synaptic marker proteins; 3) the number of synaptophysin-immunopositive puncta; 4) the number of dendritic spines per length; 5) the density of synaptic ultrastructures; 6) ultrastructures similar to synapse perforation. Increment in these indices occurred -10 days after forskolin-application and outlasted the following weeks. The increase in postsynaptic potential depended not only on the times of forskolin-application but also the interval between the applications. The increase was blocked by inhibitors of PKA and MAPK. These results indicate that late-phase LTP is not long-term plasticity.
The cultured brain slice aseptically exposed to chemical stimulants should serve as a good model system for the analysis of persistent synaptogenesis possibly related to long-term memory in mammalian CNS. Less
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