Thornton for Mbnl2GT4 mice, L. Ranum for manuscript comments, and the Research Resource Network Japan for human brain samples. This work was supported by grants from the NIH (NS058901 to M.S.S; K99GM95713 to C.Z.; NS34389 to R.B.D.; GM084317 to M.A.; and AG014979, AG037984, and AG036800 to T.C.F.), the McKnight Brain Research Foundation (T.C.F.), the MDA (4280 to M.S.S., 135140 to M.A.), the NCNP Japan (22-7 to K.J.), and the Japanese Ministry of Health, Labour, and Welfare (22-118 to T.K.). “
“The neocortex is strikingly uniform, with extensive repetition of a limited number of circuit motifs (Douglas and Martin, 1998). But neocortical circuits

are also highly diverse, consisting of a multitude of cell types with widely differing intrinsic and morphological properties (Ascoli et al., 2008; Markram et al., 2004). Specific and differential Small molecule library datasheet properties of synaptic connections themselves have also been reported (Galarreta and Hestrin, 1998; Markram et al., 1998; Reyes et al., 1998), for example, between neocortical pyramidal cells (PCs) or between PCs and Martinotti cell (MC) interneurons (INs). In the hippocampus, it was recently reported that

postsynaptic molecular properties determine long-term plasticity in certain inhibitory cell types (Nissen et al., 2010), indicating that synaptic molecular markers may in fact define Venetoclax nmr IN types (Ascoli et al., 2008). NMDA receptors (NMDARs) are nonspecific cationic ionotropic glutamate receptors that, in the classical view, play important roles in dendritic integration (Schiller et al., 2000), excitatory transmission (Lisman et al., 2008; Salt, 1986), and coincidence detection for Hebbian plasticity (Yuste and Denk, 1995). Here, the characteristic dual dependence of NMDARs on presynaptically released glutamate and on postsynaptic depolarization is key to their proper functioning in these roles (Ascher and Nowak, 1988; MacDermott et al., 1986), which means NMDARs need to be located postsynaptically. But there is also increasing evidence for the existence of putatively presynaptic NMDARs (preNMDARs) (Corlew et al., 2008), e.g., in spinal cord (Bardoni et al.,

2004), cerebellum (Casado et al., 2002; Duguid and Smart, 2004), amygdala (Humeau et al., 2003), and cortex (Berretta and Jones, 1996; Sjöström et al., 2003). These preNMDARs can impact both spontaneous and evoked neurotransmission in the short and intermediate Dipeptidyl peptidase term (Bardoni et al., 2004; Duguid and Smart, 2004; Sjöström et al., 2003) but may also play a role in the induction of long-term plasticity (Casado et al., 2002; Humeau et al., 2003; Sjöström et al., 2003). Their presynaptic location, however, is peculiar, as it seems to render, e.g., NMDAR-based detection of coincident activity in connected neurons impossible without additional signaling from the postsynaptic side (Duguid and Sjöström, 2006). This suggests that preNMDARs may also serve other, presently unknown functions, pertinent to the functioning of the microcircuit.