, 2011 and Younger et al., 2013). This observation was extended by recent work using the ENaC channel blocker benzamil to acutely disrupt presynaptic homeostasis. Benzamil was applied to the NMJ of animals lacking the muscle-specific GluRIIA glutamate receptor subunit, a perturbation that is persistent throughout development and induces Tyrosine Kinase Inhibitor Library solubility dmso presynaptic homeostasis. Benzamil erased the expression of presynaptic homeostasis, leaving behind a synapse with unpotentiated wild-type release and wild-type anatomy ( Younger et al., 2013). Together, these data demonstrate that presynaptic homeostasis is uncoupled from the

mechanisms that achieve anatomical and physiological NMJ growth. One possibility is that presynaptic homeostasis is only induced developmentally when a cellular set point differs from ongoing activity. If the set point is developmentally programmed to change along with the maturation

of cell fate, then a developmental change in cellular function could occur without the induction of homeostatic plasticity. Veliparib clinical trial In the mammalian CNS, homeostatic and developmental plasticity coexist. This is nicely documented in a binocular region of visual cortex after monocular deprivation (Mrsic-Flogel et al., 2007). When cells receive input predominantly from an open eye, deprived eye input is diminished, consistent with classical synaptic competition. However, when cells receive input predominantly from the deprived eye, these inputs are strengthened, consistent with homeostatic plasticity. Binocular deprivation also induces Phenibut homeostatic synaptic strengthening. Although these processes coexist, it remains unclear whether homeostatic plasticity normally participates in ocular dominance independent of an experimental perturbation such as eye suturing. In other examples, cell-autonomous suppression of neural

activity has been shown to induce changes in synaptic connectivity as well as homeostatic plasticity, but the effects are separated in time (Burrone et al., 2002). There are emerging molecular links between homeostatic plasticity and neurological disease. The schizophrenia-associated gene dysbindin was isolated in a forward genetic screen for mutations that block presynaptic homeostasis ( Dickman and Davis, 2009). Homer and mGluR signaling are implicated in mouse models of fragile X syndrome ( Ronesi et al., 2012), as is retinoic acid ( Soden and Chen, 2010). Others have speculated the involvement of disrupted homeostatic signaling in posttraumatic epilepsy ( Houweling et al., 2005), Rett syndrome ( Ramocki and Zoghbi, 2008 and Qiu et al., 2012), and autism spectrum disorders ( Bourgeron, 2009). A wealth of information is emerging regarding rare de novo mutations with strong effects in autism spectrum disorders and it is possible that further associations with homeostatic plasticity will emerge ( Murdoch and State, 2013).