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Degree

Doctor of Philosophy, Case Western Reserve University, Neurosciences, 2007.

Abstract

RGS2, one of the small members of the regulator of G protein signaling (RGS) family, is highly expressed in brain and regulates Gi/o as well as Gq coupled receptor pathways. RGS2 modulates anxiety, aggression and blood pressure in mice suggesting that RGS2 regulates synaptic circuits underlying animal physiology and behavior. How RGS2 in brain influences synaptic activity was unknown. We therefore analyzed the synaptic function of RGS2 in hippocampal neurons and the system function of RGS2 in the serotonergic system by comparing electrophysiological recordings from RGS2 knock-out and wild type mice. Our study from hippocampal neurons provides a general mechanism of the action of the RGS family containing RGS2 by demonstrating that RGS2 increases synaptic vesicle release by down-regulating the Gi/o mediated presynaptic Ca2+ channel inhibition. Our results from serotonergic neurons reveal that loss of RGS2 leads to changes in the physiological properties of the neurons, including changes in membrane potential and spontaneous firing which are mediated by increased G protein activity in these neurons. Our results suggest that RGS2 regulates precisely the firing and output of serotonergic neurons in the brain, which provides for the first time an explanation of how regulation of RGS2 expression can modulate the function of neuronal circuits underlying behavior.

Subject Headings

Biology, Neuroscience

Keywords

RGS2; serotonergic; neurons; Gi/o; serotonergic neurons; RGS; PROTEIN

Advisor

Stefan Herlitze

Pages

159p.

Document number: case1175703706
Permalink: http://rave.ohiolink.edu/etdc/view?acc_num=case1175703706

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