Prefrontal projections to the thalamic nucleus reuniens mediate fear extinction. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Ramanathan, Karthik; Jin, Jingji; Giustino, Thomas; Payne, Martin; Maren, Stephen
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 12
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-06970-z
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract 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. Previous work has shown that the thalamic nucleus reuniens (RE) is involved in memory and emotion. Here the authors report that the RE and its inputs from the medial prefrontal cortex are indispensable for the top-down inhibition of fear memories after extinction.