Biology subjects

Kottke, B. W.

Publications and source records attributed to Kottke, B. W..

2 recordsLinked to original sources

bioRxiv2024

Early and widespread engagement of the cerebellum during hippocampal epileptiform activity

Despite research illustrating the cerebellum may be a critical circuit element in processes beyond motor control, and growing evidence for a role of the cerebellum in a range of neurological disorders, including the epilepsies, remarkably little is known about cerebellar engagement during seizures. We therefore implemented a novel method for repeated widefield calcium imaging of the cerebellum in awake, chronically epileptic mice. We found widespread changes in cerebellar Purkinje cell activity during temporal lobe seizures. Changes were noted in the anterior and posterior cerebellum (lobules IV-VII), along the midline (vermis), and both ipsilaterally and contralaterally (in the simplex and Crus I) to the seizure focus. This was true for both overtly behavioral seizures and for hippocampal seizures that remained electrographic only -- arguing against cerebellar modulation simply reflecting motor components. Moreover, even brief interictal spikes produced widespread alterations in cerebellar activity. Perhaps most remarkably, changes in the cerebellum also occurred prior to any noticeable change in the hippocampal electrographic recordings. Together these results underscore the relevance of the cerebellum with respect to seizure networks, warranting a more consistent consideration of the cerebellum in epilepsy.

neuroscience↗

bioRxiv2023

Mesoscale Ca2+ imaging reveals networks of Purkinje cell dendritic and somatic modulation, with divergent roles of activity versus correlation during behavior

A major challenge in cerebellar physiology is determining how the stereotypic, conserved circuitry of the cerebellar cortex, with its dominant parasagittal and transverse architectures, underlies its fundamental computations and contributions to behavior. To interrogate Purkinje cell dynamics at this parasagittal and transverse spatial scale, we implemented a novel approach for awake, chronic, wide-field Ca2+ imaging of the cerebellar cortex. We observe two functionally and spatially distinct Purkinje cell networks, reflecting their dendritic and somatic activities, respectively. Both dendritic and somatic networks exhibit bilateral, widespread activation during behavior, but with diverse patterns of spatial correlations occurring primarily along the parasagittal and transverse directions, consistent with the main geometry of the cerebellar cortex. Somatic network correlation dynamics are robustly modulated by prediction errors, and even reflect ultimate behavioral outcomes. These results provide a novel link between cerebellar structure and function, with the correlation dynamics of Purkinje cell activity a key feature.

neuroscience↗