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bioRxiv · 10.1101/567628

A Role for Gαz in regulating seizure susceptibility

Hultman, R.·Boms, O.·Mague, S. D.·Hughes, D.·Nadler, V.·Dzirasa, K.·Casey, P. J.
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Abstract

Much about the molecular mechanisms underlying seizure susceptibility remains unknown. A number of studies have indicated that the neurotrophic factor BDNF plays an important role in mediating seizure susceptibility. Recently, we found that the heterotrimeric G - protein, Gz, which is known to endogenously couple to monoaminergic receptors, such as serotonin, norepinephrine and dopamine receptors, regulates BDNF-induced signaling and development in cortical neurons. Interestingly, several of the receptors that Gz endogenously couples to have also been shown to be associated with seizure phenotypes (5HT1A-serotonin and D2 dopamine). Here we characterized seizure susceptibility in Gz-null mice, behaviorally and electrographically, finding that Gz-null mice have increased seizure susceptibility using a modified version of the pilocarpine model of status epilepticus. Local field potential (LFP) data recorded from six brain regions-amygdala, dorsal hippocampus, ventral hippocampus, motor cortex, somatosensory cortex, and thalamus-showed robust electrographic seizure activity for Gz-null mice compared with low or no seizure activity in wild-type controls.

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Hultman, R., Boms, O., Mague, S. D., Hughes, D., Nadler, V., Dzirasa, K., Casey, P. J.. 2019-03-06. A Role for Gαz in regulating seizure susceptibility. https://doi.org/10.1101/567628

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