Optogenetic Inhibition of Medial Prefrontal Cortex–Pontine Nuclei Projections During the Stimulus-free Trace Interval Impairs Temporal Associative Motor Learning

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The medial prefrontal cortex (mPFC) is closely involved in many higher-order cognitive functions, including learning to associate temporally discontiguous events (called temporal associative learning). However, direct evidence for the role of mPFC and the neural pathway underlying modulation of temporal associative motor learning is sparse. Here, we show that optogenetic inhibition of the mPFC or its axon terminals at the pontine nuclei (PN) during trace intervals or whole trial period significantly impaired the trace eyeblink conditioning (TEC), but had no significant effects on TEC during the conditioned stimulus or intertrial interval period. Our results suggest that activities associated with the mPFC-PN projection during trace intervals is crucial for trace associative motor learning. This finding is of great importance in understanding the mechanisms and the relevant neural pathways underlying mPFC modulation of temporal associative motor learning.