Authors :
Presenting Author: Martha Streng, PhD – University of Minnesota
Benjamin Kottke, B.A. – University of Minnesota; Emma Wasserman, B.A. – University of Minnesota; Lucas Zecker, B.A. – University of Minnesota; Linh Luong, B.A. – University of Minnesota; Timothy Ebner, PhD – University of Minnesota; Esther Krook-Magnuson, PhD – University of Minnesota
Rationale:
Despite not being traditionally associated with epilepsy or seizures, the cerebellum has emerged as a potentially critical node in seizure networks. Chronic epilepsy is associated with cerebellar alterations including disrupted functional and structural connectivity, volume, and perfusion. During seizures themselves, alterations in cerebellar blood flow and phase locking of single cell activity occur, but it is unclear how these alterations influence ongoing cerebellar processing. It is critical to understand exactly how seizures and chronic epilepsy influence cerebellar dynamics, as cerebellar deficits can coincide with cognitive impairments and can even predict sudden unexplained death in epilepsy (SUDEP).
Methods:
To address these major questions, we recently developed a novel method for chronic mesoscale recordings of the of the cerebellar cortex in head fixed, behaving mice using cerebellar windows. Using PcP2-GCaMP6s mice, the activity of Purkinje cells, the primary output neurons of the cerebellar cortex, is recorded across lobules IV-VII of both vermis, simplex, and Crus I regions of the cerebellar cortex. Combined with simultaneous hippocampal LFP recordings in mice that had previously received unilateral intrahippocampal kainic acid injections, our approach allows for the quantification of Purkinje cell modulation during chronic, spontaneous hippocampal electrographic seizures.
Results:
We find that hippocampal electrographic seizures evoke widespread alterations in Purkinje cell activity throughout the dorsal cerebellar cortex. Importantly, these seizures lack any overt motor symptoms, indicating that cerebellar modulation cannot be attributed to pure changes in motor output. In addition to being engaged by the seizures themselves, changes in cerebellar activity precede hippocampal seizures, with dramatic reductions in synchrony observed between cerebellar networks during preictal periods.
Conclusions: Together, these results indicate that hippocampal seizures can profoundly influence cerebellar activity, and suggest that alterations in cerebellar dynamics might potentially serve as a predictor of seizure onset in temporal lobe epilepsy.
Funding: This work was supported in part by NIH K99NS121274 (MLS), P30 DA048742 (TJE), an American Epilepsy Society Postdoctoral Fellowship (MLS), NIH R01-NS112518 (EKM), NIH R01-NS111028 (TJE), a University of Minnesota McKnight Land-Grant Professorship award (EKM) The Winston and Maxine Wallin Neuroscience Discovery Fund Award (EKM), and the University of Minnesota’s MnDRIVE (Minnesota’s Discovery, Research and Innovation Economy) initiative (EKM).