Activity-dependent site-specific changes of glutamate receptor composition in vivo

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The subunit composition of postsynaptic non–NMDA-type glutamate receptors (GluRs) determines the function and trafficking of the receptor. Changes in GluR composition have been implicated in the homeostasis of neuronal excitability and synaptic plasticity underlying learning. Here, we imaged GluRs in vivo during the formation of new postsynaptic densities (PSDs) at Drosophila neuromuscular junctions coexpressing GluRIIA and GluRIIB subunits. GluR composition was independently regulated at directly neighboring PSDs on a submicron scale. Immature PSDs typically had large amounts of GluRIIA and small amounts of GluRIIB. During subsequent PSD maturation, however, the GluRIIA/GluRIIB composition changed and became more balanced. Reducing presynaptic glutamate release increased GluRIIA, but decreased GluRIIB incorporation. Moreover, the maturation of GluR composition correlated in a site-specific manner with the level of Bruchpilot, an active zone protein that is essential for mature glutamate release. Thus, we show that an activity-dependent, site-specific control of GluR composition can contribute to match pre- and postsynaptic assembly.

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Figure 1: GFP-labeled GluRIIA and GluRIIB expressed from genomic constructs are fully functional.
Figure 2: Patch-clamp recordings of NMJs expressing only GluRIIAGFP or GluRIIBGFP.
Figure 3: In vivo imaging of GluR composition during PSD maturation of developing Drosophila NMJs.
Figure 4: FRAP of GluRIIA and GluRIIB during synapse formation and maturation.
Figure 5: The BRP-dependent release component controls the maturation of GluR composition.
Figure 6: Influence of intracellular C-terminal domains on FRAP behavior in vivo.
Figure 7: Control of GluR composition and structural plasticity at the NMJ.


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We would like to thank D.E. Featherstone for help with establishing patch-clamp recordings from Drosophila embryos and A. DiAntonio for fly stocks. This work was supported by grants from the Deutsche Forschungsgemeinschaft to S.J.S. (SI849/2-1 and 2-2, TP A16/SFB 406, TP B25/SFB581, SFB487) and to M.H. (HE 2621/4-1 and TP B22/SFB 581), and by formel.1 grants to S.H. and R.J.K. from the Medical Faculty of the University of Leipzig.

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Correspondence to Stephan J Sigrist.

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Schmid, A., Hallermann, S., Kittel, R. et al. Activity-dependent site-specific changes of glutamate receptor composition in vivo. Nat Neurosci 11, 659–666 (2008) doi:10.1038/nn.2122

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