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CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala

Nature Neuroscience volume 12, pages 14381443 (2009) | Download Citation

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Abstract

The mechanisms that determine how information is allocated to specific regions and cells in the brain are important for memory capacity, storage and retrieval, but are poorly understood. We manipulated CREB in a subset of lateral amygdala neurons in mice with a modified herpes simplex virus (HSV) and reversibly inactivated transfected neurons with the Drosophila allatostatin G protein–coupled receptor (AlstR)/ligand system. We found that inactivation of the neurons transfected with HSV-CREB during training disrupted memory for tone conditioning, whereas inactivation of a similar proportion of transfected control neurons did not. Whole-cell recordings of fluorescently tagged transfected neurons revealed that neurons with higher CREB levels are more excitable than neighboring neurons and showed larger synaptic efficacy changes following conditioning. Our findings demonstrate that CREB modulates the allocation of fear memory to specific cells in lateral amygdala and suggest that neuronal excitability is important in this process.

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Acknowledgements

We thank T. Carvalho, Y.-S. Lee, P. Golshani, D. Buonomano, B. Wiltgen, W. Tan, J. Shobe, J. Feldman and J. Guzowski for helpful advice, E. Callaway for AlstR cDNA and K. Cai for technical support. This work was supported by grants from the US National Institutes of Health (P50-MH0779720 and R37-AG13622) to A.J.S. and a Marie Curie Outgoing fellowship of the European Commission (PIOF-GA-2008-219622) to P.P.

Author information

Author notes

    • Yu Zhou

    Present address: Department of Physiology, Medical College of Qingdao University, Qingdao, China.

Affiliations

  1. Department of Neurobiology, University of California Los Angeles, Los Angeles, California, USA.

    • Yu Zhou
    • , Jaejoon Won
    • , Mikael Guzman Karlsson
    • , Miou Zhou
    • , Thomas Rogerson
    • , Jayaprakash Balaji
    •  & Alcino J Silva
  2. Semel Institute, University of California Los Angeles, Los Angeles, California, USA.

    • Yu Zhou
    • , Jaejoon Won
    • , Mikael Guzman Karlsson
    • , Miou Zhou
    • , Thomas Rogerson
    • , Jayaprakash Balaji
    •  & Alcino J Silva
  3. Department of Psychology, University of California Los Angeles, Los Angeles, California, USA.

    • Yu Zhou
    • , Jaejoon Won
    • , Mikael Guzman Karlsson
    • , Miou Zhou
    • , Thomas Rogerson
    • , Jayaprakash Balaji
    •  & Alcino J Silva
  4. Brain Research Institute, University of California Los Angeles, Los Angeles, California, USA.

    • Yu Zhou
    • , Jaejoon Won
    • , Mikael Guzman Karlsson
    • , Miou Zhou
    • , Thomas Rogerson
    • , Jayaprakash Balaji
    •  & Alcino J Silva
  5. Picower Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Rachael Neve
  6. Computational Biology Laboratory, Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology Hellas, Vassilika Vouton, Heraklion, Crete, Greece.

    • Panayiota Poirazi

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Contributions

Y.Z., J.W. and A.J.S. designed the experiments. Y.Z., J.W., M.G.K. and T.R. carried out the behavioral experiments. Y.Z. performed the patch-clamp and whole-cell recording experiments. J.W. generated the viral vectors and R.N. provided the viral preparations. M.Z. carried out the western blot analysis. Y.Z. and J.W. analyzed the data. B.J. and P.P. helped with the discussion. Y.Z and A.J.S. wrote the paper.

Corresponding author

Correspondence to Alcino J Silva.

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DOI

https://doi.org/10.1038/nn.2405