Interestingly, the authors suggest that olfactory inputs transmitted by ORNs are integrated in the antennal lobe, leading to feedback that modulates Notch activity in the ORNs. In support of this contention, they show that disrupting synaptic transmission by either the ORNs, or their local interneurons, changes the pattern of Notch activity. All told, this exciting work clearly indicates that the Notch receptor is activated in complex neuronal ensembles in response to specific sensory inputs. Nicely corroborating the fly work, we have found that in the mouse brain, Notch signaling is

this website induced by synaptic activity (Alberi et al., 2011). We show that Notch1 and its ligand Jag1 are present at the synapse, and that expression of both is increased in response to neuronal activity. In addition,

using neuronal cultures, acute hippocampal slice preparations, and an in vivo behavioral paradigm, we show that Notch1 activation is enhanced by synaptic activity. We also identified a mechanistic connection between Notch and activity-dependent neuronal gene expression by showing that Notch activation in neurons is positively regulated by the activity-induced plasticity gene Arc/Arg3.1 ( Chowdhury et al., 2006, Link et al., 1995, Lyford et al., 1995, Plath et al., 2006 and Shepherd et al., 2006). While the effect of Arc/Arg3.1 on Notch activation does not directly account for all of the effects of synaptic activity on Notch pathway components (i.e., www.selleckchem.com/products/INCB18424.html how Notch1 and Jag1 expression are increased remains unclear), this work provides valuable insight into the regulation of Notch in neurons. The existence of activity-dependent Notch signaling in both flies and mice suggests that this phenomenon is conserved and is

likely to serve an essential function Phosphoglycerate kinase in neurons. Indeed, our work has shown that conditional deletion of Notch1 in pyramidal neurons of the postnatal hippocampus led to alterations in spine density and morphology, as well as reduced LTP and LTD. Consistent with defects in synaptic function, at the behavioral level, loss of Notch1 resulted in deficits in the processing of novel acquired information. Our Notch1 deletion results are in line with previous work of others (Costa et al., 2003, Saura et al., 2004 and Wang et al., 2004). However, by circumventing the potential contribution of developmental defects in two of those studies (Costa et al., 2003 and Wang et al., 2004), and the lack of Notch pathway specificity in another (Saura et al., 2004), we have added strong support to the idea that Notch is essential for synaptic plasticity, learning, and memory in mammals. Based upon the study by Lieber and colleagues, and previous work on Notch and long-term memory formation in flies (Ge et al.