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

Nat Neurosci. 2009 Nov;12(11):1438-43. doi: 10.1038/nn.2405. Epub 2009 Sep 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Amygdala / cytology*
  • Analysis of Variance
  • Animals
  • Biophysics
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Drosophila
  • Drosophila Proteins / genetics
  • Electric Stimulation
  • Fear
  • Gene Transfer Techniques
  • Green Fluorescent Proteins / genetics
  • Hormone Antagonists / pharmacology
  • In Vitro Techniques
  • Memory / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropeptides / pharmacology
  • Patch-Clamp Techniques / methods
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, Neuropeptide / genetics
  • Simplexvirus / genetics


  • AstA-R1 protein, Drosophila
  • Cyclic AMP Response Element-Binding Protein
  • Drosophila Proteins
  • Hormone Antagonists
  • Neuropeptides
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • allatostatin
  • Green Fluorescent Proteins