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Published Online January 24, 2008
Science DOI: 10.1126/science.1151120

Reports

Submitted on September 28, 2007
Accepted on January 11, 2008

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

Toshiaki Nakashiba 1, Jennie Z. Young 1, Thomas J. McHugh 1, Derek L. Buhl 1, Susumu Tonegawa 1*

1 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.
Susumu Tonegawa , E-mail: tonegawa{at}mit.edu

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Direct Cortical Inputs Erase Long-Term Potentiation at Schaffer Collateral Synapses.
Y. Izumi and C. F. Zorumski (2008)
J. Neurosci. 28, 9557-9563
   Abstract »    Full Text »    PDF »
Inaugural Article: Parallel memory processing by the CA1 region of the dorsal hippocampus and the basolateral amygdala.
M. Cammarota, L. R. Bevilaqua, J. I. Rossato, R. H. Lima, J. H. Medina, and I. Izquierdo (2008)
PNAS 105, 10279-10284
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)