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


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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Figure 1: Selective and reversible modulation of a set of genetically targeted lateral amygdala neurons.
Figure 2: Local infusion of allatostatin selectively impairs auditory fear memory in HSV-CREB mice.
Figure 3: Allatostatin does not disrupt conditioning in HSV-CREB mice established before viral transfection.
Figure 4: HSV-CREB neurons in conditioned mice show increased synaptic efficacy.
Figure 5: CREB increases neuronal excitability in transfected lateral amygdala neurons.
Figure 6: HSV-CREB changes the input-output function of transfected lateral amygdala neurons.


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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




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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Zhou, Y., Won, J., Karlsson, M. et al. CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala. Nat Neurosci 12, 1438–1443 (2009).

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