RT Journal Article
SR Electronic
T1 A Role for Gαz in regulating seizure susceptibility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 567628
DO 10.1101/567628
A1 Rainbo Hultman
A1 Okechi Boms
A1 Stephen Mague
A1 Dalton Hughes
A1 Victor Nadler
A1 Kafui Dzirasa
A1 Patrick J. Casey
YR 2019
UL http://biorxiv.org/content/early/2019/03/06/567628.abstract
AB 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.Abbreviations usedBDNFbrain-derived neurotrophic factorCNScentral nervous systemNEnorepinephrinDAdopamine5-HTserotonin