These changes largely

selleck arise via Ca2+ entry through NMDARs, enabling NMDAR activation to encode changes in neuronal activity. Additionally, another type of synaptic plasticity has been identified in multiple areas of the CNS, where changes in neuronal activity induce a switch in AMPAR subtype (Liu and Savtchouk, 2012). Strengthening or weakening of synapses occurs not through changes in number of AMPARs but by alteration of AMPAR channel properties (Savtchouk and Liu, 2011). AMPARs are heteromeric tetramers made up of four basic subunits (GluA1–GluA4). Receptor trafficking, protein interactions, and specific channel properties are dependent upon subunit composition. Of these subunits, the GluA2 subunit

is critical in determining AMPAR signaling properties. AMPARs lacking the GluA2 subunit are permeable to Ca2+, exhibit a high single channel conductance, and are blocked by polyamines, resulting in an inwardly rectifying I-V relationship (Bowie and Mayer, 1995; Swanson et al., 1997; Washburn et al., 1997). Changes in AMPAR subtype are generated via alterations in neuronal activity that accompany development, sensory deprivation, emotional stress, addiction, pain, disease, and high-frequency synaptic stimulation (Bellone and Lüscher, 2005; Clem and Barth, 2006; Grooms et al., 2000; Liu et al., 2010; Nagy et al., 2004; Opitz et al., 2000; Osswald et al., 2007; Vikman http://www.selleckchem.com/products/at13387.html et al., 2008; Xia et al., 2007). Excitatory synapses on all functional classes (ON, OFF, and ON-OFF) of retinal ganglion cells (RGCs) utilize both GluA2-lacking, Ca2+-permeable AMPARs (CP-AMPARs) and GluA2-containing, Ca2+-impermeable AMPARs (CI-AMPARs) and NMDARs (Chen and Diamond, 2002; Diamond and Copenhagen, 1993; Lukasiewicz PD184352 (CI-1040) et al., 1997; Xia et al., 2007). As the retina encounters a dynamically changing visual scene, these synapses experience a wide range of neural activity. Multiple mechanisms of fast and slow synaptic and cell-intrinsic adaptation exist to contend with the changing light environment,

yet very little evidence for plasticity of glutamate receptors exists in the retina. However, recently, AMPARs on ON RGCs were shown to undergo activity-dependent regulation. In ON RGCs, 8 hr of light deprivation generated a switch in surface AMPAR composition from primarily CI-AMPARs to CP-AMPARs (Xia et al., 2006, 2007). These results suggest that AMPARs are subjected to more regulation than previously thought and leave open the possibility for regulation by increasing activity. NMDARs on RGCs are located perisynaptically (Chen and Diamond, 2002; Sagdullaev et al., 2006; Zhang and Diamond, 2009) and may be uniquely suited for detecting and integrating changes in synaptic input in these cells, since receptors located outside the synapse are not activated by single quantum of transmitter release but require a burst of activity to cause “spillover.