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Case Western Reserve University researchers find how a protein regulates anxiety

Case Western Reserve University : 16 January, 2007  (Technical Article)
What makes us anxious? For the first time, researchers from Case Western Reserve University demonstrated how one of the members of the regulator of the G signaling proteins called RGS2 found in the brain influences the synaptic activity of neuronal circuits involved in regulation of anxiety.
'Among the RGS family, RGS2 plays a prominent role in the brain but until now it was not known how it functioned,' said Stefan Herlitze, Assistant Professor of Neurosciences. He is among the researchers to report their discovery of how RGS2 functions in the Neuron article, 'RGS2 determines short-term plasticity in hippocampal neurons by regulating Gi/o mediated inhibition of presynaptic Ca2+ channels.'

Also working on the National Institutes of Health-funded study were Jing Han, Melanie Mark, Xiang Li, Sayumi Waka from Case's department of neurosciences, with Jen Rettig from the Department of Physiology at Saarland University in Homburg, Germany.

RGS2 acts as a gatekeeper to neuronal activity. The role that RGS2 has in the up and down regulation of neural transmissions became evident during studies when mice without the RGS2 protein revealed a decrease in synaptic strength and exhibited an increase in anxiety but lower aggression when compared with a group of wild-type mice. The study was performed in hippocampal neurons in each group of mice.

What the Case neuroscientists found is that the RGS2 influences the paired-pulse ratios that is the amount of signals, which are transmitted at the synapses. When RGS2 is absence, the researchers found that the paired-pulse facilitation is increased leading to reduced synaptic release. This effect is surprisingly mediated via G protein coupled receptors of the Gi/o type and not the Gq type, which had been the favorable target of RGS2 in other cell types.

'These studies suggest that RGS2 is involved in regulating neuronal circuits underlying animal behavior via setting the basal activity of the Gi/o pathway at the synaptic terminals of the brain,' said the researchers.
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