Interestingly, although

Aoto et al. (2008) demonstrate that RA mimics mini blockade in driving protein synthesis-dependent postsynaptic recruitment of GluA1 to synapses and enhancing mEPSC amplitude, it had no effect on mEPSC frequency suggesting a selective role in postsynaptic compensation. Together with our findings, these results suggest that distinct releasable factors may be engaged for homeostatic adjustment of pre- and postsynaptic function. For homeostatic forms of plasticity induced by coincident blockade of APs and NMDARs, multiple studies have demonstrated enhanced synthesis of GluA1 in dendrites (Ju et al., 2004 and Sutton et al., 2006) or synaptic fractions (Aoto et al., 2008) and the incorporation of GluA2-lacking receptors at synapses click here (Ju et al., 2004, Sutton et al.,

2006 and Aoto et al., 2008). By contrast, blockade of APs alone induces a slower form of postsynaptic compensation characterized find protocol by enhanced expression of GluA2-containing AMPARs at synapses (Turrigiano et al., 1998, Wierenga et al., 2005 and Sutton et al., 2006), possibly owing to a decrease in receptor removal and an accumulation of existing synaptic receptors (e.g., O’Brien et al., 1998, Ehlers, 2003 and Ibata et al., 2008). These results support the notion that spontaneous and AP-mediated neurotransmission engage unique signaling pathways in neurons (Sutton et al., 2007 and Atasoy et al., 2008) and that miniature synaptic events in these neurons play an important role in the acute homeostatic regulation of synaptic strength. Frank et al. (2006) identified a similar role for spontaneous neurotransmission in rapid homeostatic adjustment of synaptic function at the Drosophila neuromuscular junction, suggesting Non-specific serine/threonine protein kinase that this role for miniature events may be conserved across

different synapse classes and species. In a similar vein, Thiagarajan et al. (2005) demonstrated the synaptic recruitment of GluA2-lacking AMPARs in response to chronic (∼24 hr) AMPAR blockade, suggesting that loss of AMPAR activity also engages mechanisms that recruit GluA2-lacking AMPARs to synapses. Our results extend these observations by demonstrating that AMPAR blockade induces rapid postsynaptic recruitment of GluA1 that is dependent on new protein synthesis. Moreover, we found that regardless of the presence or absence of background spiking, the increase in synaptic GluA1 and mEPSC amplitude induced by AMPAR blockade is indistinguishable. These results have two important implications. First, they demonstrate that although AP blockade reveals the functional impact of miniature neurotransmission (see also Sutton et al., 2006), this role extends to conditions where background spiking is permissive.