Prefrontal projections
to the nucleus reuniens signal
behavioral relevance of stimuli
during associative learning

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Xiaotian Yu, Fasika Jembere, Kaori Takehara-Nishiuchi, Scientific Report.

 

Sitting at home on a cold and rainy day, a bright flash momentarily illuminates your entire room, you’ve seen this many times before, and mentally you prepare for what’s about to come next. Then, as on cue, the loud cacophony of thunder bellows from above. Through countless experiences of this pairing, lightning then thunder, you’ve formed a temporal association between the bright flash and the roar that occurs moments later. The ability to form these temporal associations comes naturally to many animals and is dependent on intercommunication between the medial prefrontal cortex (mPFC) and hippocampus (HPC). However, as the mPFC lacks direct excitatory projections to the HPC, it remains unclear as to how exactly mPFC output reaches the HPC. Possessing strong reciprocal connections to both the PFC and HPC, the nucleus reuniens of the midline thalamus (RE) is thought to route information between these two regions. In this study, we show that the ability to form an association between a neutral stimulus and an upcoming aversive event is dependent on proper RE function. Furthermore, the gradual formation of this associative memory across days is accompanied by changes in mPFC output to the RE. This change was not seen for mPFC output to other thalamic regions lacking connections with the HPC, such as the mediodorsal thalamus. Collectively, our findings suggest that the mPFC sends information critical for the formation of temporal associative memories to the RE, further supporting the notion that mPFC to HPC communication occurs via the RE.