Functional anatomy of neural circuits regulating fear and extinction

Ewelina Knapska, Matylda Macias, Marta Mikosz, Aleksandra Nowak, Dorota Owczarek, Marcin Wawrzyniak, Marcelina Pieprzyk, Iwona A. Cymerman, Tomasz Werka, Morgan Sheng, Stephen Maren, Jacek Jaworski, Leszek Kaczmarek

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17093-17098
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number42
DOIs
StatePublished - Oct 16 2012
Externally publishedYes

Keywords

  • Gene expression
  • Hippocampus
  • Learning and memory
  • Prefrontal cortex

ASJC Scopus subject areas

  • General

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