HippoBellum: Acute cerebellar modulation alters hippocampal dynamics and function

Here we examine what effects acute manipulation of the cerebellum, a canonically motor structure, can have on the hippocampus, a canonically cognitive structure. In male and female mice, acute perturbation of the cerebellar vermis (lobule 4/5) or simplex produced reliable and specific effects in hippocampal function at cellular, population, and behavioral levels, including evoked local field potentials, increased hippocampal cFos expression, and altered CA1 calcium event rate, amplitudes, and correlated activity. We additionally noted a selective deficit on an object location memory task, which requires objection-location pairing. We therefore combined cerebellar optogenetic stimulation and CA1 calcium imaging with an object-exploration task, and found that cerebellar stimulation reduced the representation of place fields near objects, and prevented a shift in representation to the novel location when an object was moved. Together, these results clearly demonstrate that acute modulation of the cerebellum alters hippocampal function, and further illustrates that the cerebellum can influence cognitive domains. SIGNIFICANCE STATEMENT The cerebellum, a canonically motor-related structure, is being increasingly recognized for its influence on nonmotor functions and structures. The hippocampus is a brain region critical for cognitive functions, such as episodic memory and spatial navigation. To investigate how modulation of the cerebellum may impact the hippocampus, we stimulated two sites of the cerebellar cortex and examined hippocampal function at multiple levels. We found that cerebellar stimulation strongly modulates hippocampal activity, disrupts spatial memory, and alters object-location processing. Therefore, a canonically cognitive brain area, the hippocampus, is sensitive to cerebellar modulation.