Abstract
Modification of synaptic strength in the mammalian central nervous system (CNS) occurs at both pre- and postsynaptic sites1,2. However, because postsynaptic receptors are likely to be saturated by released transmitter, an increase in the number of active postsynaptic receptors may be a more efficient way of strengthening synaptic efficacy3,4,5,6,7. But there has been no evidence for a rapid recruitment of neurotransmitter receptors to the postsynaptic membrane in the CNS. Here we report that insulin causes the type A γ-aminobutyric acid (GABAA) receptor, the principal receptor that mediates synaptic inhibition in the CNS8, to translocate rapidly from the intracellular compartment to the plasma membrane in transfected HEK 293 cells, and that this relocation requires the β2 subunit of the GABAA receptor. In CNS neurons, insulin increases the expression of GABAA receptors on the postsynaptic and dendritic membranes. We found that insulin increases the number of functional postsynaptic GABAA receptors, thereby increasing the amplitude of the GABAA-receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) without altering their time course. These results provide evidence for a rapid recruitment of functional receptors to the postsynaptic plasma membrane, suggesting a fundamental mechanism for the generation of synaptic plasticity.
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Acknowledgements
We thank M. Wojtowicz and F. Dorri for assistance with slice experiments; C. Kaufman and D. Gunnersen for GABAA receptor β2 and γ2 subunit cDNAs; J. H. Steinbach for the α1FLAGcDNA; D. Carter for the 4D4 cells; C. C. Yip for insulin; and M. W. Salter for helpful comments on the manuscript. This work was supported by the Medical Research Council of Canada and Neuroscience Network of Centers of Excellence of Canada. Y.T.W. is a research scholar of the Heart and Stroke Foundation of Canada/Ontario; Z.G.X. is a MRC-NCE fellow and W.Y.L. is a NCE fellow. H.Y.M. is supported by a studentship from the Canadian Foundation for the Study of Infant Death.
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Wan, Q., Xiong, Z., Man, H. et al. Recruitment of functional GABAA receptors to postsynaptic domains by insulin. Nature 388, 686–690 (1997). https://doi.org/10.1038/41792
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DOI: https://doi.org/10.1038/41792
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