The cerebellum contributes to tonic-clonic seizures by altering neuronal activity in the ventral posteromedial nucleus (VPM) of the thalamus

Abstract

Thalamo-cortical networks are central to seizures, yet its unclear how these circuits initiate the seizures. Here, we test the hypothesis that a facial region of the thalamus, the VPM, is a source of convulsive, tonic-clonic seizures. We devised an in vivo optogenetic mouse model to elicit tonic-clonic seizures by driving convergent input to the VPM. With viral tracing, we show dense cerebellar and cerebral cortical afferent input to the VPM. Lidocaine microinfusions into the cerebellar nuclei selectively block seizure initiation. We perform single-unit electrophysiology recordings during awake, convulsive seizures to define the local activity of thalamic neurons before, during, and after seizure onset. We find highly dynamic activity with biphasic properties, raising the possibility that heterogenous activity patterns promote seizures. These data reveal the VPM as a source of tonic-clonic seizures, with cerebellar input providing the predominant signals.