Prefrontal projections to the thalamic nucleus reuniens mediate fear extinction

Nat Commun. 2018 Oct 30;9(1):4527. doi: 10.1038/s41467-018-06970-z.


The thalamic nucleus reuniens (RE) receives dense projections from the medial prefrontal cortex (mPFC), interconnects the mPFC and hippocampus, and may serve a pivotal role in regulating emotional learning and memory. Here we show that the RE and its mPFC afferents are critical for the extinction of Pavlovian fear memories in rats. Pharmacological inactivation of the RE during extinction learning or retrieval increases freezing to an extinguished conditioned stimulus (CS); renewal of fear outside the extinction context was unaffected. Suppression of fear in the extinction context is associated with an increase in c-fos expression and spike firing in RE neurons to the extinguished CS. The role for the RE in suppressing extinguished fear requires the mPFC, insofar as pharmacogenetically silencing mPFC to RE projections impairs the expression of extinction memory. These results reveal that mPFC-RE circuits inhibit the expression of fear, a function that is essential for adaptive emotional regulation.

Publication types

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

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology*
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology*
  • Fear*
  • Freezing Reaction, Cataleptic
  • GABA-A Receptor Agonists / pharmacology
  • Learning / physiology
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Midline Thalamic Nuclei / drug effects
  • Midline Thalamic Nuclei / metabolism
  • Midline Thalamic Nuclei / physiology*
  • Muscimol / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Long-Evans


  • GABA-A Receptor Agonists
  • Proto-Oncogene Proteins c-fos
  • Muscimol