0 NA) water immersion objective. SpH was excited at 488 nm using a Polychrome IV monochromator (Till Photonics). Electrophysiological and FM2-10 based measurements were carried out as previously described (Rozas et al., 2011) (see Supplemental Experimental Procedures for details). We followed the procedures previously described (Rozas et al., 2011) (see Supplemental Experimental Procedures for details). Muscles in resting

conditions or after stimulation (180 s at 30 Hz) were processed for conventional transmission electron microscopy (for details, see Supplemental Experimental Procedures). Images were taken on a CM-10 (Philips) electron microscope with Veleta (Olympus) camera controlled by iTEM platform (Olympus SIS). This work has been Target Selective Inhibitor Library cell assay supported by Spanish MINECO (Juan de la Cierva and FPU Programs, BES2008-002858, BFU2007-66008, BFU2010-15713, ERA-NET NEURON EUI2009-04084, CTQ2009-14431/BQU, SAF2010-20822-C02), Junta de Andalucía (P06-CVI-02392,

P07-CVI-02854), Xunta de Galicia (INCITE09 209 084PR), HFSP (RGP 0045/2002-C and CDA0032/2005-C), Instituto de Salud Carlos III and FEDER. We are grateful to T.C. Südhof, W.J. Betz, G. Alvarez de Toledo, W. Regehr, and F.J. Urbano for critical reading of previous or recent versions of the manuscript and insightful comments; M.L. Montesinos, R. Ruiz, O. Uchitel, and F.J. Urbano for technical advice; L. Tabares for loan of equipment; J. Lopez-Barneo for support and advice; T.C. Südhof and P. McPherson for antibodies; Alejandro Arroyo and M. Carmen Rivero for excellent technical assistance; G. Cantero for help with

genotyping; I. Benito for help with mouse husbandry learn more and C.O. Pintado for transgenesis. Part of the study performed at CITIUS (University of Seville). “
“At both vertebrate and invertebrate synapses, alterations in synaptic activity trigger homeostatic responses that modulate synaptic strength; it appears that these homeostatic responses manifest as changes in postsynaptic receptor expression as well as retrograde regulation of transmitter release (Branco et al., 2008, Cai et al., 2008, Davis, 2006, Goold and Nicoll, 2010, Jakawich et al., 2010, Petersen et al., 1997, Sandrock et al., 1997, Stellwagen and Malenka, 2006, Sutton and Schuman, 2006, Turrigiano and Nelson, 2004 and Turrigiano et al., 1998). Postsynaptic translation plays an important role in mafosfamide local changes in postsynaptic receptor expression (Bidinosti et al., 2010, Costa-Mattioli et al., 2009, Menon et al., 2004, Sigrist et al., 2000 and Sutton et al., 2007); however, we know little about whether translational mechanisms also participate in the retrograde control of neurotransmitter release. At the Drosophila larval neuromuscular junction (NMJ), loss or inhibition of glutamate receptor subunit IIA (GluRIIA) triggers a robust retrograde increase in neurotransmitter release to compensate for the reduction in postsynaptic receptor function ( Frank et al., 2006 and Petersen et al., 1997).