Electrophysiology of Gαz protein as a mediator for seizure susceptibility

Abstract

Seizures are marked by a state of irregular, recurrent neuronal activity in the brain. Seizures are typical across a wide range of disorders including epilepsy, autism, and they are high comorbidity with anxiety disorders.

In the mouse model, increased levels of brain-derived neurotrophic factor (BDNF) have been linked to increased seizure susceptibility. Gαz, a member of the G-protein family, is important for the negative regulation of BDNF; Gαz-null show more BDNF-regulated axon growth. We postulated that since Gαz-null mice have increased levels of BDNF, Gαz might play a role in mediating seizure susceptibility. A previous study from our lab showed that Gαz -null mice were in fact more susceptible to seizures than wildtype (WT) mice.

This study was conducted to characterize neuronal seizure activity and progression across different brain regions for this genetic model. Electrodes were implanted into the brains of WT and Gαz -null mice to record the local field potential (LFPs), proxy for relative activity, during induced seizure by the pilocarpine (180mg/kg) drug. LFP data was recorded simultaneously from 6 brain regions: amygdala, dorsal hippocampus, motor cortex, somatosensory cortex, ventral hippocampus, and thalamus.

The Gαz -null mice had more severe seizure behavior and more robust electrographic activity in comparison to the WT group. The site of seizure onset and progression for the WT group closely matches the pattern from other studies, while the Gαz -null mice showed a novel pattern. The behavioral and electrographic results confirm the role of Gαz in mediating seizure severity and susceptibility; further studies will be needed to confirm the seizure progression pattern noted for the WT and Gαz-null groups.