Cortico-cerebellar coherence and causal connectivity during slow-wave activity

Cerebral cortical slow-wave activity (SWA) is prominent during sleep and also during ketamine-induced anesthesia. SWA in electroencephalogram (EEG) recordings is closely linked to prominent fluctuations between up- and down-states in the membrane potential of pyramidal neurons. However, little is known about how the cerebellum is linked into SWA and whether slow cortical oscillations influence sensory cerebellar responses. To examine these issues, we simultaneously recorded EEG activity from the cerebral cortex (SI, MI, and supplementary motor area (SMA)), local field potentials at the input stage of cerebellar processing in the cerebellar granule cell layer (GCL) and inferior olive (IO), and single unit activity at the output stage of the cerebellum in the deep cerebellar nuclei (DCN). We found that in ketamine-anesthetized rats, SWA was synchronized between all recorded cortical areas and was phase locked with local field potentials of the GCL, IO and single unit activity in the DCN. We also found that cortical up-states are linked to activation of GCL neurons but to inhibition of cerebellar output from the DCN, with the latter an effect likely mediated by Purkinje cells. A partial coherence analysis showed further that a large portion of SWA shared between GCL and DCN was transmitted from the cortex, since the coherence shared between GCL and DCN was diminished when the effect of cortical activity was subtracted. To determine the causal flow of information between structures, a directed transfer function was calculated between the simultaneous activities of SI, MI, SMA, GCL and DCN. This analysis demonstrated that the primary direction of information flow was from cortex to the cerebellum and that SI had a stronger influence than other cortical areas on DCN activity. The strong functional connectivity with SI in particular is in agreement with previous findings of a strong cortical component in cerebellar sensory responses.