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A molecular correlate of memory and amnesia in the hippocampus


Memory consolidation in humans and other species is profoundly disrupted by lesions of either the medial temporal lobes or regions of the thalamus1,2,3. It has been proposed that these structures regulate the neuronal gene expression necessary for long-term memory4. Evidence suggests that long-term memory formation requires the activity of members of the cAMP response element (CRE) binding protein (CREB) transcription factor family5,6, and that CRE-regulated genes are expressed in the hippocampus in response to inhibitory avoidance training7,8. Here we show that lesions of the fornix, a massive fiber bundle connecting the hippocampus with the septum and hypothalamus, specifically disrupt both consolidation of inhibitory avoidance memory and CREB-mediated responses in the hippocampus. We propose that inputs passing through the fornix regulate this memory consolidation by regulating CREB-mediated gene expression in hippocampal neurons.

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Figure 1: Fornix lesions produce impairment on the inhibitory avoidance task.
Figure 2: Inhibitory avoidance training increases hippocampal CREB phosphorylation in normal rats but not in rats with fornix lesions.
Figure 3: CREB phosphorylation after inhibitory avoidance learning is induced mainly in CA1 and dentate gyrus (DG).


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This work was supported by the Whitehall Foundation (grant # F97-07), the Charles A. Dana Foundation and the Howard Hughes Medical Institute. The authors thank Deborah Brenner, Stephane Nedelec, Eric Sklar, Suzanne Meagher and Arnold Heynen for their assistance.

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Correspondence to Cristina M. Alberini.

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Taubenfeld, S., Wiig, K., Bear, M. et al. A molecular correlate of memory and amnesia in the hippocampus. Nat Neurosci 2, 309–310 (1999).

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