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Transgenic Inhibition of Synaptic Transmission Reveals Role of CA3 Output in Hippocampal Learning

by: Toshiaki Nakashiba, Jennie Z Young, Thomas J Mchugh, Derek L Buhl, Susumu Tonegawa
Science (24 January 2008), 1151120.


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The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information from the entorhinal cortex [->] dentate gyrus [->] CA3 [->] CA1 [->] entorhinal cortex) and the monosynaptic pathway (which connects entorhinal cortex [->] CA1 [->] entorhinal cortex). We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid, one-trial contextual learning, for pattern completionbased memory recall and for spatial tuning of CA1 cells. 10.1126/science.1151120


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