Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear

Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear. Here we show that after extinction training, coherent theta oscillations (6–9 Hz) in the HPC and mPFC are correlated with the suppression of conditioned freezing in male and female rats. Inactivation of the nucleus reuniens (RE), a thalamic hub interconnecting the mPFC and HPC, reduces extinction-related Fos expression in both the mPFC and HPC, dampens mPFC-HPC theta coherence, and impairs extinction retrieval. Conversely, theta-paced optogenetic stimulation of RE augments fear suppression and reduces relapse of extinguished fear. Collectively, these results demonstrate a role for RE in coordinating mPFC-HPC interactions to suppress fear memories after extinction.

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All studies must disclose on these points even when the disclosure is negative.Any animals with missed targeting of either guide cannula or optic fiber tips were excluded from all analyses.
All reported findings were replicated as all experiments were ran as two separate cohorts of animals, except for Fig. 6 which was ran as single cohort of animals.
All between-subject groups were randomly assigned prior to beginning of behavioral testing.Within-subjects test order groups for drug and optogenetic manipulations were determined following the final extinction day to ensure no group differences.
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