Y. Kiyama and T. Manabe offered valuable insights on behavioral tests. Y. Oikawa and K. Takatsuka provided technical support on superresolution imaging. T. Nakano and J.R. Whickens advised us on stereotaxic surgery. T. Abe and S. Aizawa produced the PCDH17−/− mice. J. Miyazaki supplied CAG-Cre transgenic mice. T. Akagi furnished the pCX4-bsr vector. R.F. Whittier and S.D. Aird gave CP868596 the

manuscript a critical reading, and members of our laboratory offered valuable comments. This work was supported by Grants-in-Aid for Scientific Research 23700411 (N.H.), 20220006 (M.T.), 19100005 (M.W.), 21220006 (M.K.), and 17013021 and 19390070 (T.Y.), the Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior), the Comprehensive Brain Science Network (Development of Molecular Profiling of Brain), and the Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. “
“Neurons are arranged in ordered circuits which underlie information processing in the brain. The specificity of synaptic connections between partner neurons depends on pathfinding decisions during axon growth, which are SNS-032 price mediated by axon guidance cues (Dickson, 2002).

Upon the arrival of axons in their target area, there is an initial period of synaptogenesis, followed by a later, often experience-dependent period of synapse re-modeling and synapse maturation, in which exuberant connections are pruned, and remaining connections acquire their specific synaptic strength and sets of synaptic plasticities (Sanes and Yamagata, 2009; Shen and Scheiffele, 2010). Therefore, axon pathfinding decisions, followed by later programs of synaptogenesis and synapse maturation, ensure the specificity of synaptic wiring in Dichloromethane dehalogenase the brain. Synaptic connections in the CNS greatly vary in terms of their transmission strength (Sherman and Guillery, 1998; Walmsley et al., 1998). It might be expected that synapses formed by axons that contact neurons in distant, and often

contralateral target areas, should have a strong influence on the action potential (AP) firing of their postsynaptic neurons (“driver” or “relay” type of synapses; Sherman and Guillery, 1998). Genetic ablation of axon guidance proteins or of their receptors has been shown to lead to aberrant wiring of axons, particularly at the midline (Brose et al., 1999; Fazeli et al., 1997; Kidd et al., 1999; Serafini et al., 1996; for review see Chédotal, 2011). However, it has remained relatively unexplored whether misguided axons can form functionally normal synapses. It could be expected that feedback mechanisms exist that suppress the function of synapses formed in inappropriate target areas, or on the wrong side of the brain, but the existence of such mechanisms is largely unknown. The calyx of Held synapse in the mammalian central auditory system is an ideal model to address this question.