Regulating Synaptic Strength

Science's STKE  12 Sep 2006:
Vol. 2006, Issue 352, pp. tw314
DOI: 10.1126/stke.3522006tw314

Regulator of G protein signaling (RGS) proteins stimulate the intrinsic guanosine triphosphatase activity of heterotrimeric guanine nucleotide-binding proteins (G proteins) that terminates G protein signaling. RGS2, which is abundant in brain, inhibits signaling through both Gi/o and Gq pathways and influences anxiety and aggression in mice. Han et al. recorded excitatory postsynaptic currents (EPSCs) from cultured hippocampal neurons making autaptic synapses and determined the relative amplitudes of EPSCs elicited 50 msec apart. Exogenous expression of RGS2 in rat or mouse neurons reduced the ratio of the amplitude of the second EPSC relative to that of the first (paired-pulse ratio, PPR), yielding paired-pulse depression. In contrast, neurons from mice lacking RGS2 (RGS2–/– mice) showed an increase in the relative amplitude of the second EPSC, yielding substantial paired-pulse facilitation. Pharmacological analysis indicated that the effects of RGS2 on PPR were mediated through Gi/o but not Gq, a conclusion substantiated by experiments involving an RGS2 mutant that suppressed Gq signaling but acted as a dominant-negative in the Gi/o pathway.Changes in PPR may result from differences in vesicle release probability and, indeed, release probability was reduced in RGS2–/– mice compared with wild type. Analysis of Ca2+ currents indicated a greater degree of basal Ca2+ channel inhibition in RGS2–/– neurons (likely due to increased abundance of free Gβγ). The authors conclude that RGS2 regulates Ca2+ influx through presynaptic Ca2+ channels, and thereby synaptic strength, by decreasing basal activity of Gi/o and that regulation of RGS2 abundance could thus provide a mechanism for modulating synaptic efficacy.

J. Han, M. D. Mark, X. Li, M. Xie, S. Waka, J. Rettig, S. Herlitze, RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating Gi/o-mediated inhibition of presynaptic Ca2+ channels. Neuron 51, 575-586 (2006). [PubMed]