CEREBELLO-PREFRONTAL COMMUNICATION IN A RODENT MODEL OF SCHIZOPHRENIA

Time processing is essential for behavior and decision-making. These processes are disrupted in schizophrenia and may underlie cognitive deficits. Temporal processing relies on a distributed network, the cerebello-thalamo-prefrontal pathway. The prefrontal cortex (PFC) supports goal-directed control, and the cerebellum organizes actions in time. To investigate cerebello-prefrontal communication, we used the Synapsin II knock-out (SynII KO) mouse model of schizophrenia. Synapsin II is a synaptic protein involved in regulating neurotransmitter release and synaptic transmission. We developed a cued–reward interval timing behavioral task in which mice received a visual cue after variable delays. Timing was not required but could be used to anticipate and optimize performance. In 20% of trials, the temporal interval was varied, with short and long delays. Reaction times and success rates were measured. Mice were implanted with multi-unit electrodes in PFC and cerebellum.
Control and SynII KO mice learned the task to a similar level (~65% success). In controls, long delays reduced reaction times, increased success rates, and local field potential correlated with the task in cerebellum and PFC. Beta and theta band amplitudes increased during the delay, and the slope of this increase correlated with success rate. In SynII KO mice, delay variations affected reaction times but not success rates. Furthermore, anticipatory oscillations were amplified but uncoupled from success rate.
These results suggest altered cerebello-prefrontal communication in SynII KO mice. They further support the idea that cerebello–prefrontal coordination translates anticipatory neural dynamics into behavior, and its disruption could contribute to temporal deficits in schizophrenia.