| It is well known that repeated revision is a much better way to learn than last-minute cramming. This observation has a correlate in the study of synaptic plasticity, where spaced rather than massed stimuli are more effective in producing synaptic change. What is the mechanism for the synapse to prefer one kind of input over the other ? We have studied pattern selectivity in the hippocampal CA3-CA1 synapse on the time-scale of minutes using electrophysiological, biochemical and computer simulation methods. In accordance with numerous behavioural findings, we observed a peak in LTP at for repetitive stimuli at an interval of around 10 minutes. Using simulations we narrowed down candidate molecules for this process, and then tested for their biochemical activity. We find that mitogen associated protein kinase (MAPK) but not calcium-calmodulin activated type II kinase (CaMKII) correlates with this pattern selectivity. Interestingly, there are multiple possible synaptic signaling mechanism s that may give rise to selectivity in this time-range. A possible feedback mechanism involves resonance of stimulus interval with propagation delays around a feedback loop involving MAPK. A distinct feedforward mechanism involves the buildup of a constitutively active kinase that activates MAPK, with a time-period that matches the tuning peak. Yet another mechanism could involve up-regulation of an inhibitory phosphatase that terminates the MAPK activity. We consider the possible drawbacks and implications of these different mechanisms and present some recent intriguing findings that may further test our understanding of such pattern selectivity.
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Date： |
Dec. 8 (Wed) |
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Time： |
17:00-18:00 |
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Place： |
Faculty of Medicine bldg, 13F, 1303 (3rd seminar room) |
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Host： |
Haruhiko Bito (03-5841-3559, hbito@m.u-tokyo.ac.jp)
Shinya Kuroda (03-5841-4697,skuroda@is.s.u-tokyo.ac.jp) |
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