MESODIENCEPHALIC CONTROL OF OLIVOCEREBELLAR SYSTEM DURING DISCRIMINATION LEARNING

Learning how to discriminate between sensory cues and differentially act upon them is essential for survival. Whereas cerebral input to cerebellum via the pontine mossy fiber system has been shown to participate in execution of decision-making, the contribution of the olivary climbing fiber system in this process remains elusive. Here, we investigated the hypothesis that the descending relay from the mesodiencephalic junction (MDJ) to the inferior olive (IO) plays a critical role in the acquisition of sensory discrimination learning in a go/no-go task in mice. Chemogenetic inhibition of the MDJ-IO pathway during training disrupted discrimination learning. The level and temporal shift of activity of MDJ neurons and downstream climbing fibers correlated with the level of acquisition, pointing to a direct role in learning to make choices. Notably, inhibiting the MDJ-IO pathway in overly trained mice did not affect choice performance or task execution, underscoring a dissociation between acquiring new cognitive associations and performing learned behaviors. Moreover, optogenetic stimulation of the MDJ in well-trained, but not naive mice, elicited a "go"-like licking motor response exclusively in mice that had successfully mastered the task ("Good learners"). Conversely, "Poor learners" and naive controls showed no motor output upon stimulation, despite confirmed physiological activation of the pathway. Our findings establish the MDJ-IO pathway as a key player in the acquisition of procedural decision-making, facilitating discrimination learning and unleashing associated motor engrams in response to cognitive cues.