Functional anatomy of neural circuits regulating fear and extinction

Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17093-8. doi: 10.1073/pnas.1202087109. Epub 2012 Oct 1.


The memory of fear extinction is context dependent: fear that is suppressed in one context readily renews in another. Understanding of the underlying neuronal circuits is, therefore, of considerable clinical relevance for anxiety disorders. Prefrontal cortical and hippocampal inputs to the amygdala have recently been shown to regulate the retrieval of fear memories, but the cellular organization of these projections remains unclear. By using anterograde tracing in a transgenic rat in which neurons express a dendritically-targeted PSD-95:Venus fusion protein under the control of a c-fos promoter, we found that, during the retrieval of extinction memory, the dominant input to active neurons in the lateral amygdala was from the infralimbic cortex, whereas the retrieval of fear memory was associated with greater hippocampal and prelimbic inputs. This pattern of retrieval-related afferent input was absent in the central nucleus of the amygdala. Our data show functional anatomy of neural circuits regulating fear and extinction, providing a framework for therapeutic manipulations of these circuits.

Publication types

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

MeSH terms

  • Amygdala / physiology*
  • Analysis of Variance
  • Animals
  • Bacterial Proteins / metabolism
  • Conditioning, Psychological
  • DNA Primers / genetics
  • Disks Large Homolog 4 Protein
  • Extinction, Psychological / physiology*
  • Fear / physiology*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Limbic System / physiology*
  • Luminescent Proteins / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Memory / physiology*
  • Microscopy, Confocal
  • Neural Pathways / anatomy & histology*
  • Neural Pathways / physiology
  • Rats
  • Rats, Transgenic
  • Recombinant Fusion Proteins / metabolism*
  • Video Recording


  • Bacterial Proteins
  • DNA Primers
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • yellow fluorescent protein, Bacteria