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Transgenic Inhibition of Synaptic Transmission Reveals Role of CA3 Output in Hippocampal Learning
Toshiaki Nakashiba,Jennie Z. Young,Thomas J. McHugh,Derek L. Buhl,Susumu Tonegawa*
The hippocampus is an area of the brain involved in learningand memory. It contains parallel excitatory pathways referredto as the trisynaptic pathway (which carries information asfollows: entorhinal cortex dentate gyrus CA3 CA1 entorhinalcortex) and the monosynaptic pathway (entorhinal cortex CA1 entorhinal cortex). We developed a generally applicable tetanustoxin–based method for transgenic mice that permits inducibleand reversible inhibition of synaptic transmission and appliedit to the trisynaptic pathway while preserving transmissionin the monosynaptic pathway. We found that synaptic output fromCA3 in the trisynaptic pathway is dispensable and the shortmonosynaptic pathway is sufficient for incremental spatial learning.In contrast, the full trisynaptic pathway containing CA3 isrequired for rapid one-trial contextual learning, for patterncompletion–based memory recall, and for spatial tuningof CA1 cells.
The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, RIKEN-MIT Neuroscience Research Center, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
* To whom correspondence should be addressed. E-mail: tonegawa{at}mit.edu
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