Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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).


  1. Scoville, W. B. & Milner, B. J. Neurol. Neurosurg. Psychiatry 20, 11–21 (1957).

    CAS  Article  Google Scholar 

  2. de Castro, J. & Hall, T. W. Physiol. Psychol. 3, 201–204 (1975).

    Article  Google Scholar 

  3. Squire, L. R. Memory and Brain (Oxford, New York, 1987).

    Google Scholar 

  4. Bear, M. F. Nature 385, 481–482 (1997).

    CAS  Article  Google Scholar 

  5. Yin, J. C. P. et al. Cell 79, 49–58 (1994).

    CAS  Article  Google Scholar 

  6. Silva, A. J., Kogan, J. H., Frankland, P. W. & Kida, S. Annu. Rev. Neurosci. 21, 127–148 (1998).

    CAS  Article  Google Scholar 

  7. Bernabeu, R. et al. Proc. Natl. Acad. Sci. USA 94, 7041–7046 (1997).

    CAS  Article  Google Scholar 

  8. Impey, S. et al. Nat. Neurosci. 1, 595– 601 (1998).

    CAS  Article  Google Scholar 

  9. Yin, J. C. P., Del Vecchio, M., Zhou, H. & Tully, T. Cell 81, 107–115 (1995).

    CAS  Article  Google Scholar 

  10. Bourtchuladze, R. et al. Cell 79, 59–68 (1994).

    CAS  Article  Google Scholar 

  11. Montminy, M. Annu. Rev. Biochem. 66, 807–822 (1997).

    CAS  Article  Google Scholar 

  12. Frey, U. & Morris, R. G. M. Nature 385, 533–536 (1997).

    CAS  Article  Google Scholar 

  13. Baldi, E., Lorenzini, C. A., Sacchetti, B., Tassoni, G. & Bucherelli, C. Brain Res. 799, 270–277 (1998).

    CAS  Article  Google Scholar 

  14. Lorenzini, C. A., Baldi, E., Bucherelli, C., Sacchetti, B. & Tassoni, G. Brain Res. 730, 32–39 (1996).

    CAS  Article  Google Scholar 

  15. Wiig, K. A., Cooper, L. N. & Bear, M. F. Learn. Mem. 3, 313– 325 (1996).

    CAS  Article  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Cristina M. Alberini.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing