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Role for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory


A dialogue between the hippocampus and the neocortex is thought to underlie the formation, consolidation and retrieval of episodic memories1,2,3,4, although the nature of this cortico-hippocampal communication is poorly understood. Using selective electrolytic lesions in rats, here we examined the role of the direct entorhinal projection (temporoammonic, TA) to the hippocampal area CA1 in short-term (24 hours) and long-term (four weeks) spatial memory in the Morris water maze. When short-term memory was examined, both sham- and TA-lesioned animals showed a significant preference for the target quadrant. When re-tested four weeks later, sham-lesioned animals exhibited long-term memory; in contrast, the TA-lesioned animals no longer showed target quadrant preference. Many long-lasting memories require a process called consolidation, which involves the exchange of information between the cortex and hippocampus3,5,6. The disruption of long-term memory by the TA lesion could reflect a requirement for TA input during either the acquisition or consolidation of long-term memory. To distinguish between these possibilities, we trained animals, verified their spatial memory 24 hours later, and then subjected trained animals to TA lesions. TA-lesioned animals still exhibited a deficit in long-term memory, indicating a disruption of consolidation. Animals in which the TA lesion was delayed by three weeks, however, showed a significant preference for the target quadrant, indicating that the memory had already been adequately consolidated at the time of the delayed lesion. These results indicate that, after learning, ongoing cortical input conveyed by the TA path is required to consolidate long-term spatial memory.

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Figure 1: Specificity of TA lesions.
Figure 2: TA-lesioned animals exhibit deficits in long-term, but not short-term spatial memory.
Figure 3: Disruption of the TA path 24 h after learning resulted in deficits in long-term spatial memory.
Figure 4: Disruption of the TA path three weeks after learning does not abolish long-term spatial memory.


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We thank T. Siapas, G. Laurent, M. Sutton and other members of the Schuman laboratory for discussions. This work was supported by the Fundacao para a Ciencia e Technologia (FCT)—Portugal and the Howard Hughes Medical Institute.

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Correspondence to Erin M. Schuman.

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Supplementary information

Supplementary Figure 1

Lesion data for animals included in the behavioural analyses shown in Figures 2 and 3. (JPG 97 kb)

Supplementary Figure 2

More TA lesion data for all animals included in the behavioural analyses. (JPG 117 kb)

Supplementary Figure 3

Visible platform data for all animals in all experiments. In addition, probe trial data for animals that received complete hippocampal lesions, and the sham and TA-lesioned animals probe trial at 24 hrs post-training. (JPG 110 kb)

Supplementary Methods

Methods used for surgical procedures, lesion execution and assessment and electrophysiology. (PDF 13 kb)

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Remondes, M., Schuman, E. Role for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory. Nature 431, 699–703 (2004).

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