MEDIAL PREFRONTAL CORTEX ACTIVITY PREDICTS BEHAVIOURAL SPECIFICITY AND TRANSFER IN VISUAL CLASSICAL CONDITIONING<S>​</S>

[Aims] The medial prefrontal cortex (mPFC) develops sensory responses to a visual stimulus after learning a visuomotor association. However, it is unclear whether these stimulus-driven responses represent the sensorimotor association, the value of the stimulus, or both.
[Methods] We addressed this question by investigating visual responses in the mPFC during classical conditioning. We recorded activity across the dorsal cortex with longitudinal widefield calcium imaging while mice underwent two-stage classical conditioning. In stage 1, which was designed to mimic a previously used sensorimotor task, a visual stimulus moving from the periphery to the centre signalled the availability of a reward. In stage 2, the peripheral stimulus itself signalled the availability of a reward while remaining static. After training on each day, we passively presented stimuli without rewards.
[Results] After learning stage 1 with the moving stimulus, mice bifurcated into two groups: those with bilateral mPFC responses to the rewarded stimulus (mPFC+) and those without (mPFC-). Both groups showed equivalent on-target anticipatory licking in stage 1. However, mPFC- animals exhibited more off-target licking during inter-trial intervals and non-rewarded stimulus presentation. Critically, only mPFC+ animals successfully learned stage 2 with the static stimulus, indicating that mPFC activity during stage 1 predicts the ability to remap the same stimulus-reward association when sensory features change.
[Conclusions] mPFC sensory responses are not necessary for initial stimulus-reward learning, but their presence is associated with increased behavioural specificity and flexibility. This suggests mPFC encodes stimulus-specific reward predictions that support adaptive behaviour beyond simple associative learning.