PMID- 23189042 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121129 LR - 20211021 IS - 1662-5110 (Electronic) IS - 1662-5110 (Linking) VI - 6 DP - 2012 TI - Molecular mechanism of parallel fiber-Purkinje cell synapse formation. PG - 90 LID - 10.3389/fncir.2012.00090 [doi] LID - 90 AB - The cerebellum receives two excitatory afferents, the climbing fiber (CF) and the mossy fiber-parallel fiber (PF) pathway, both converging onto Purkinje cells (PCs) that are the sole neurons sending outputs from the cerebellar cortex. Glutamate receptor delta2 (GluRdelta2) is expressed selectively in cerebellar PCs and localized exclusively at the PF-PC synapses. We found that a significant number of PC spines lack synaptic contacts with PF terminals and some of residual PF-PC synapses show mismatching between pre- and postsynaptic specializations in conventional and conditional GluRdelta2 knockout mice. Studies with mutant mice revealed that in addition to PF-PC synapse formation, GluRdelta2 is essential for synaptic plasticity, motor learning, and the restriction of CF territory. GluRdelta2 regulates synapse formation through the amino-terminal domain, while the control of synaptic plasticity, motor learning, and CF territory is mediated through the carboxyl-terminal domain. Thus, GluRdelta2 is the molecule that bridges synapse formation and motor learning. We found that the trans-synaptic interaction of postsynaptic GluRdelta2 and presynaptic neurexins (NRXNs) through cerebellin 1 (Cbln1) mediates PF-PC synapse formation. The synaptogenic triad is composed of one molecule of tetrameric GluRdelta2, two molecules of hexameric Cbln1 and four molecules of monomeric NRXN. Thus, GluRdelta2 triggers synapse formation by clustering four NRXNs. These findings provide a molecular insight into the mechanism of synapse formation in the brain. FAU - Mishina, Masayoshi AU - Mishina M AD - Brain Science Laboratory, The Research Organization of Science and Technology, Ritsumeikan University Shiga, Japan ; Molecular Neurobiology and Pharmacology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan. FAU - Uemura, Takeshi AU - Uemura T FAU - Yasumura, Misato AU - Yasumura M FAU - Yoshida, Tomoyuki AU - Yoshida T LA - eng PT - Journal Article DEP - 20121123 PL - Switzerland TA - Front Neural Circuits JT - Frontiers in neural circuits JID - 101477940 PMC - PMC3505014 OTO - NOTNLM OT - Purkinje cell OT - glutamate receptor delta2 OT - motor learning OT - neurexin OT - parallel fiber OT - synapse formation EDAT- 2012/11/29 06:00 MHDA- 2012/11/29 06:01 PMCR- 2012/01/01 CRDT- 2012/11/29 06:00 PHST- 2012/08/30 00:00 [received] PHST- 2012/11/02 00:00 [accepted] PHST- 2012/11/29 06:00 [entrez] PHST- 2012/11/29 06:00 [pubmed] PHST- 2012/11/29 06:01 [medline] PHST- 2012/01/01 00:00 [pmc-release] AID - 10.3389/fncir.2012.00090 [doi] PST - epublish SO - Front Neural Circuits. 2012 Nov 23;6:90. doi: 10.3389/fncir.2012.00090. eCollection 2012.