How the cerebellum and prefrontal cortex cooperate during trace eyeblinking conditioning

Several data have demonstrated that during the widely used experimental paradigm for studying associative learning, trace eye blinking conditioning (TEBC), there is a strong interaction between cerebellum and medial prefrontal cortex (mPFC). Despite this evidence, the neural mechanisms underlying this interaction are still not clear. Here, we propose a neurophysiologically plausible computational model to address this issue. The model is constrained on the basis of two critical anatomo-physiological features: (i) the cerebello-cortical organization through two circuits, respectively, targeting M1 and mPFC; (ii) the different timing in the plasticity mechanisms of these parallel circuits produced by the granule cells time sensitivity according to which different subpopulations are active at different moments during conditioned stimuli. The computer simulations run with the model suggest that these features are critical to understand how the cooperation between cerebellum and mPFC supports motor areas during TEBC. In particular, a greater trace interval produces greater plasticity changes at the slow path synapses involving mPFC with respect to plasticity changes at the fast path involving M1. As a consequence, the greater is the trace interval, the stronger is the mPFC involvement. The model has been validated by reproducing data collected through recent real mice experiments.