Prefrontal cortex projections to the nucleus reuniens suppress freezing following two-way signaled avoidance training.
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ABSTRACT:
SUBMITTER: Moscarello JM
PROVIDER: S-EPMC7029723 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:The reuniens nucleus in the midline thalamus projects to the medial prefrontal cortex (mPFC) and the hippocampus, and has been suggested to modulate interactions between these regions, such as spindle-ripple correlations during sleep and theta band coherence during exploratory behavior. Feedback from the hippocampus to the nucleus reuniens has received less attention but has the potential to influence thalamocortical networks as a function of hippocampal activation. We used the retrograde tracer cholera toxin B conjugated to two fluorophores to study thalamic projections to the dorsal and ventral hippocampus and to the prelimbic and infralimbic subregions of mPFC. We also examined the feedback connections from the hippocampus to reuniens. The goal was to evaluate the anatomical basis for direct coordination between reuniens, mPFC, and hippocampus by looking for double-labeled cells in reuniens and hippocampus. In confirmation of previous reports, the nucleus reuniens was the origin of most thalamic afferents to the dorsal hippocampus, whereas both reuniens and the lateral dorsal nucleus projected to ventral hippocampus. Feedback from hippocampus to reuniens originated primarily in the dorsal and ventral subiculum. Thalamic cells with collaterals to mPFC and hippocampus were found in reuniens, across its anteroposterior axis, and represented, on average, about 8 % of the labeled cells in reuniens. Hippocampal cells with collaterals to mPFC and reuniens were less common (~1 % of the labeled subicular cells), and located in the molecular layer of the subiculum. The results indicate that a subset of reuniens cells can directly coordinate activity in mPFC and hippocampus. Cells with collaterals in the hippocampus-reuniens-mPFC network may be important for the systems consolidation of memory traces and for theta synchronization during exploratory behavior.
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Project description:The prefrontal cortex (PFC) integrates incoming information to guide our actions. When motivation for food-seeking competes with avoidance of danger, the PFC likely plays a role in selecting the optimal choice. In platform-mediated active avoidance, rats avoid a tone-signaled footshock by stepping onto a nearby platform, delaying access to sucrose pellets. This avoidance requires prelimbic (PL) PFC, basolateral amygdala (BLA), and ventral striatum (VS). We previously showed that inhibitory tone responses of PL neurons correlate with avoidability of shock (Diehl et al., 2018). Here, we optogenetically modulated PL terminals in VS and BLA to identify PL outputs regulating avoidance. Photoactivating PL-VS projections reduced avoidance, whereas photoactivating PL-BLA projections increased avoidance. Moreover, photosilencing PL-BLA or BLA-VS projections reduced avoidance, suggesting that VS receives opposing inputs from PL and BLA. Bidirectional modulation of avoidance by PL projections to VS and BLA enables the animal to make appropriate decisions when faced with competing drives.
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