In contrast to the targeting of OSN axons, little was known about the events that lead to the formation of synapses with M/T-cell dendrites and a number of important questions were to be answered. Synaptic activity is assumed to have a critical role in stabilizing the dendrite structure 29. Once the synapse is formed, primary dendrites are selected in a competitive manner. For synapse formation, pairing of OSN axons with nearby M/T cells takes place and then post-synaptic events are initiated in M/T-cell dendrites. Multiple sets of axon sorting molecules whose expression is regulated by OR-derived OSN activity, are responsible for glomerular segregation 27.Īlthough primary projection autonomously takes place 26 even in the absence of the target OB 28, proper connections are needed with mitral/tufted (M/T) cells in the OB to make the olfactory circuit functional. In addition to these targeting processes that occur in an activity-independent manner, olfactory circuits are further refined by OSN activity. Different sets of Neuropilin (Nrp), Semaphorin (Sema), and Plexin (Plxn) molecules are known to regulate these processes 19, 21-25: A-P projection is regulated by Nrp1 and Sema3A 26, and D-V projection is by Nrp2 and Sema3F 19. D-V projection is regulated by positional information of OSNs in the OE 12-19, while A-P projection is instructed by OR molecules using cAMP as a second messenger 20, 21. During development, a coarse olfactory map is generated by a combination of dorsal-ventral (D-V) projection and anterior-posterior (A-P) projection. Since the discovery of OR genes in 1991 by Buck and Axel 1, it has well been studied how OSN axons target to the OB for glomerular map formation 12-25. This conversion enables the brain to detect and discriminate a large repertoire of odorants 11. As a given odorant interacts with multiple OR species and a given OR responds to multiple odorants2, binding signals of odor molecules detected in the olfactory epithelium (OE) are converted to a unique set of activated glomeruli, a odor map, in the OB 7, 9, 10. Furthermore, OSN axons expressing the same type of OR converge to a specific target site, glomerulus, in the olfactory bulb (OB) 6-8. It is well-established that each olfactory sensory neuron (OSN) expresses one functional OR gene in a mono-allelic manner 2-5. The mammalian olfactory system can detect a variety of odors using approximately 1,000 odorant receptor (OR) species 1. Possible roles of Sema7A/PlxnC1 signaling will be discussed in the context of olfactory circuit formation in neonates. Since other Sema molecules are known to regulate targeting of OSN axons without involving neuronal activities, Sema7A is a unique example of Sema family proteins that regulates synapse formation and dendrite selection in an activity-dependent manner. We conclude that Sema7A/PlxnC1 signaling is key for initiating synapse formation followed by dendrite selection in M/T cells. Pharmacological blocking of NMDA receptors indicated that synaptic transmission induces primary-dendrite selection after the synapses are formed. Rescue and reconstitution experiments demonstrated that interactions of Sema7A and PlxnC1 are essential to induce the post-synaptic assembly. In the knockout mice for Sema7A or PlxnC1, initiation of synapse formation is perturbed. We recently analyzed a pair of signaling molecules, Semaphorin (Sema) 7A expressed in OSN axons and its receptor Plexin (Plxn) C1 localized to M/T-cell dendrites. Odor information is then transmitted to the olfactory cortex through synapses with mitral/tufted (M/T) cells. Odorant molecules are detected by olfactory sensory neurons (OSNs) in the olfactory epithelium.
Sema7A Signaling is Essential for Activity-Dependent Synapse Formation in the Mouse Olfactory BulbġDepartment of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanĢDepartment of Brain Function, University of Fukui School of Medicine, 23-3 Shimo-aizuki, Matsuoka, Fukui 910-1193, Japan
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