Similarly, moderate changes in neuronal firing measured in visual cortex after visual deprivation can invoke homeostatic selleck kinase inhibitor plasticity, leading

to the restoration of baseline firing rates (Keck et al., 2013 and Hengen et al., 2013; see also Deeg and Aizenman, 2011). Early efforts to model homeostatic plasticity in the stomatogastric system have emphasized that multiple activity sensors are necessary to discriminate quantitative differences in neuronal firing (Liu et al., 1998). Yet, biologically, a system of coordinated sensors with the fidelity to follow neural activity remains unknown. An interesting possibility is that metabolic sensors may be employed in addition to, or in parallel with, changes in intracellular calcium. In dissociated hippocampal culture, eukaryotic elongation factor 2 (eEF2) has been implicated as a sensor that can detect disruption of glutamatergic transmission (Sutton et al., 2004 and Sutton et al., 2007). Additional work implicates a function for TOR-dependent signaling downstream of AMPA receptor blockade (Henry et al., 2012). The potential importance of this signaling system for homeostasis in vivo is emphasized in experiments demonstrating that TOR signaling is essential for balanced network excitation and inhibition (Bateup et al., 2013). The importance of TOR is also emphasized by work at the Drosophila NMJ in vivo, showing that genetic disruption

of TOR and S6 Kinase signaling blocks the sustained expression of presynaptic homeostasis ( Penney et al., Vorinostat in vivo 2012). In many systems, TOR signaling is used to detect qualitative changes in the cellular environment and, thereby, regulates cellular homeostasis and growth ( Laplante and Sabatini, 2012). As such, it is a candidate for detecting quantitative changes

Astemizole in neural function and stimulating downstream homeostatic plasticity. Synaptic scaling is expressed as a change in neurotransmitter receptor abundance. Although a great deal has been discovered about the transcription, assembly, and trafficking of glutamate receptors, the mechanisms that control receptor trafficking in a homeostatic fashion remain largely unknown. Many key issues remain to be molecularly defined, including how synaptic scaling is achieved in a cell-wide fashion with proportional effects at every active zone. Similarly, there is very little information to explain how the synaptic scaling mechanism becomes limited as neuronal firing properties are restored toward baseline, set point levels, and how the system is eventually shut off (but see Tatavarty et al., 2013). In attempting to define how the homeostatic control of glutamate receptor trafficking is achieved, it is useful to make comparisons to nonneuronal systems in which homeostatic control of surface transporters and ion channels has been defined without the added complexity of cell diversity.