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Abstract

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 as follows: entorhinal cortex → dentate gyrus → CA3 → CA1 → entorhinal cortex) and the monosynaptic pathway (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 completion–based memory recall, and for spatial tuning of CA1 cells.

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References and Notes

1
W. B. Scoville, B. Milner, J. Neuropsychiatry Clin. Neurosci.12, 103 (1957).
2
L. R. Squire, C. E. Stark, R. E. Clark, Annu. Rev. Neurosci.27, 279 (2004).
3
L. E. Jarrard, Behav. Neural Biol.60, 9 (1993).
4
D. Marr, Philos. Trans. R. Soc. London Ser. B262, 23 (1971).
5
B. L. McNaughton, R. G. M. Morris, Trends Neurosci.10, 408 (1987).
6
R. C. O'Reilly, J. L. McClelland, Hippocampus4, 661 (1994).
7
J. L. McClelland, N. H. Goddard, Hippocampus6, 654 (1996).
8
J. E. Lisman, N. A. Otmakhova, Hippocampus11, 551 (2001).
9
D. Kumaran, E. A. Maguire, Hippocampus17, 735 (2007).
10
E. T. Rolls, R. P. Kesner, Prog. Neurobiol.79, 1 (2006).
11
B. Roozendaalet al., Nat. Neurosci.4, 1169 (2001).
12
V. H. Brunet al., Science296, 2243 (2002).
13
J. Z. Tsien, P. T. Huerta, S. Tonegawa, Cell87, 1327 (1996).
14
K. Nakazawaet al., Science297, 211 (2002).
15
K. Nakazawaet al., Neuron38, 305 (2003).
16
T. J. McHughet al., Science317, 94 (2007).
17
M. Yamamotoet al., J. Neurosci.23, 6759 (2003).
18
G. Schiavoet al., Nature359, 832 (1992).
19
S. Schochet al., Science294, 1117 (2001).
20
M. Mayfordet al., Science274, 1678 (1996).
21
M. P. Witter, D. G. Amaral, in The Rat Nervous System, G. Paxinos, Ed. (Academic Press, New York, 2004), pp. 635–710.
22
K. J. Harms, A. M. Craig, J. Comp. Neurol.490, 72 (2005).
23
M. S. Fanselow, Anim. Learn. Behav.18, 264 (1990).
24
J. W. Rudy, R. C. O'Reilly, Behav. Neurosci.113, 867 (1999).
25
M. A. Wilson, B. L. McNaughton, Science261, 1055 (1993).
26
E. M. Tanet al., Neuron51, 157 (2006).
27
W. Lerchneret al., Neuron54, 35 (2007).
28
F. Zhanget al., Nature446, 633 (2007).
29
X. Han, E. S. Boyden, PLoS One2, e299 (2007).
30
A. Y. Karpova, D. G. Tervo, N. W. Gray, K. Svoboda, Neuron48, 727 (2005).
31
T. Hafting, M. Fyhn, S. Molden, M. B. Moser, E. I. Moser, Nature436, 801 (2005).
32
F. Sargoliniet al., Science312, 758 (2006).
33
S. Maren, Annu. Rev. Neurosci.24, 897 (2001).
34
S. Nishimura-Akiyoshi, K. Niimi, T. Nakashiba, S. Itohara, Proc. Natl. Acad. Sci. U.S.A.104, 14801 (2007).
35
We thank F. Bushard, C. Carr, X. Zhou, J. Derwin, A. Ogawa, C. Lovett, and M. Ragion for technical assistance; N. Arzoumanian for her help in manuscript preparation; and A. Govindarajan, S. Itohara, M. Remondes, M. Wilson, and members of the Tonegawa lab for advice and discussion. Supported by NIH grants R01-MH078821 and P50-MH58880 to S.T.

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Science
Volume 319 | Issue 5867
29 February 2008

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Submission history

Received: 28 September 2007
Accepted: 11 January 2008
Published in print: 29 February 2008

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Authors

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

Notes

* To whom correspondence should be addressed. E-mail: [email protected]

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