The Cerebellum Contributes to Generalized Seizures by Altering Activity in the Ventral Posteromedial Nucleus

Authors

Jaclyn Beckinghausen
Joshua Ortiz-Guzman
Tao Lin
Benjamin Bachman
Luis E Salazar Leon
Yu Liu
Detlef H Heck
Benjamin R Arenkiel
Roy V Sillitoe

Publication Date

7-15-2023

Journal

Communications Biology

DOI

10.1038/s42003-023-05100-w

PMID

37454228

PMCID

PMC10349834

PubMedCentral® Posted Date

6-15-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Mice, Animals, Ventral Thalamic Nuclei, Seizures, Thalamus, Cerebral Cortex, Cerebellum

Abstract

Thalamo-cortical networks are central to seizures, yet it is unclear how these circuits initiate seizures. We test whether a facial region of the thalamus, the ventral posteromedial nucleus (VPM), is a source of generalized, convulsive motor seizures and if convergent VPM input drives the behavior. To address this question, we devise an in vivo optogenetic mouse model to elicit convulsive motor seizures by driving these inputs and perform single-unit recordings during awake, convulsive seizures to define the local activity of thalamic neurons before, during, and after seizure onset. We find dynamic activity with biphasic properties, raising the possibility that heterogenous activity promotes seizures. Virus tracing identifies cerebellar and cerebral cortical afferents as robust contributors to the seizures. Of these inputs, only microinfusion of lidocaine into the cerebellar nuclei blocks seizure initiation. Our data reveal the VPM as a source of generalized convulsive seizures, with cerebellar input providing critical signals.

Comments

This article has been corrected. See Commun Biol. 2024 Feb 16;7:186.