ADVERTISEMENT
Cerebellum Identified as Source of Generalized Convulsive Seizures
The cerebellum, a part of the hindbrain responsible for motor coordination, contributes to generalized convulsive seizures by altering the activity of a specific group of neurons in the midbrain that subsequently initiates the seizures, suggests a study involving mice published online in Communications Biology.
“To our knowledge, this is the first study to implicate the cerebellum in a pathway that alters the activity of a specific group of neurons in an area called the ventral posteromedial nucleus (VPM) in the thalamus to cause generalized seizures,” said corresponding study author Roy Sillitoe, PhD, a professor at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital in Houston.
>>NEWS: No Difference in Neurodevelopmental Outcomes With Fetal Antiseizure Drug Exposure
The study used a mouse model that involved optogenetics, a technique that controls genetically manipulated neurons with light, to elicit convulsive motor seizures in the animals. Researchers found that activating neuronal inputs to the VPM, but not to other thalamic nuclei, caused severe convulsive seizures. Up to 80% of VPM neurons may alter their activity to contribute to seizure initiation and sustainment, the research team reported. The varied activity of the affected neurons suggested a high level of heterogeneity in neural responses.
Among brain regions with possible contributions, cerebellar neurons showed the greatest ability to drive seizures in the mice, the study found. Virus tracing identified robust inputs from the cerebral cortex and cerebellar regions to VPM neurons during the seizures. When researchers inhibited the activity of the cerebellar output pathway with lidocaine, however, VPM neurons ceased seizure initiation.
“These findings not only deepen our understanding of how seizures originate but are expected to have a wider impact on several neurological diseases,” Dr Sillitoe said. “Moreover, it opens up the tantalizing possibility of using cerebellar circuits as a versatile target for therapeutic interventions to treat generalized epilepsies and other neurological disorders.”
References
