These may include positive cues promoting synapse formation INCB024360 molecular weight on CA3 neurons and negative cues preventing synapse formation on CA1 neurons. We do not rule out the possibility that the number of correct synapses is refined over time through other mechanisms. In addition it is important to note that although we always

observe a highly significant bias toward correct target innervation, we also detect incorrect synapses in culture that are not normally found in the brain. This likely reflects the fact that the brain uses several mechanisms (i.e., axon guidance, specific target recognition, synapse elimination) to ensure that neural circuits form with high fidelity. The formation of specific classes of synapses requires communication between two neurons. For this reason transmembrane cell adhesion molecules that interact with the extracellular environment and transmit information inside the cell are attractive candidates for mediating specific synapse formation. The classic cadherin gene family consists of approximately 20 members, and their differential expression in the brain has raised interest in the

possibility that cadherin-mediated interactions play an important role in synaptic specificity (Arikkath and Reichardt, 2008 and Bekirov et al., 2002). However, much of our understanding of the role of cadherins at synapses is based on N-cadherin, which is broadly expressed and appears to have a general Selleckchem LGK974 role in modulating synaptogenesis, spine formation, and plasticity in response to activity (Arikkath and Reichardt, 2008, Bozdagi et al., 2004, Bozdagi et al., 2010, Mendez et al., 2010, Saglietti et al., 2007 and Togashi et al., 2002). N-cadherin is also involved in earlier events including axon guidance and laminar targeting (Inoue and Sanes, 1997, Kadowaki et al., 2007 and Poskanzer et al., 2003), and DG axons respond differentially to N-cadherin versus cadherin-8 (Bekirov et al.,

2008). Despite extensive analysis of N-cadherin function, the role of most other cadherins in synapse formation remains unknown. Cadherin-9 is unique because it is the only cadherin with highly specific expression in DG and CA3 neurons. We found that cadherin-9 is homophilic, localizes to mossy fiber synapses, and is specifically required for formation of a subset of synapses (DG synapses) in culture and in vivo. Non-specific serine/threonine protein kinase To our knowledge, this is the first direct evidence that a cadherin regulates the differentiation of a specific class of synapses. Hippocampal neurons express multiple cadherins and, therefore, it is possible that different kinds of hippocampal synapses are specified by a unique cadherin or combination of cadherins. Cadherins participate in both homophilic and heterophilic interactions, and this feature increases the diversity of synapses that may be regulated by individual cadherins (Patel et al., 2006, Shimoyama et al., 2000 and Volk et al., 1987).