title: Neuronal Nogo-A negatively regulates dendritic morphology and synaptic transmission in the cerebellum.
abstract: Neuronal signal integration as well as synaptic transmission and plasticity highly depend on the morphology of dendrites and their spines. Nogo-A is a membrane protein enriched in the adult central nervous system (CNS) myelin, where it restricts the capacity of axons to grow and regenerate after injury. Nogo-A is also expressed by certain neurons, in particular during development, but its physiological function in this cell type is less well understood. We addressed this question in the cerebellum, where Nogo-A is transitorily highly expressed in the Purkinje cells (PCs) during early postnatal development. We used general genetic ablation (KO) as well as selective overexpression of Nogo-A in PCs to analyze its effect on dendritogenesis and on the formation of their main input synapses from parallel (PFs) and climbing fibers (CFs). PC dendritic trees were larger and more complex in Nogo-A KO mice and smaller than in wild-type in Nogo-A overexpressing PCs. Nogo-A KO resulted in premature soma-to-dendrite translocation of CFs and an enlargement of the CF territory in the molecular layer during development. Although spine density was not influenced by Nogo-A, the size of postsynaptic densities of PF-PC synapses was negatively correlated with the Nogo-A expression level. Electrophysiological studies revealed that Nogo-A negatively regulates the strength of synaptic transmission at the PF-PC synapse. Thus, Nogo-A appears as a negative regulator of PC input synapses, which orchestrates cerebellar connectivity through regulation of synapse morphology and the size of the PC dendritic tree.
authors.affiliation: Brain Research Institute, University of Zürich, 8057 Zürich, Switzerland. marija-magdalena.petrinovic@roche.com
authors.forename: Marija M
authors.initials: MM
authors.lastname: Petrinovic
authors.forename: Raphael
authors.initials: R
authors.lastname: Hourez
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Aloy
authors.forename: Gregoire
authors.initials: G
authors.lastname: Dewarrat
authors.forename: David
authors.initials: D
authors.lastname: Gall
authors.forename: Oliver
authors.initials: O
authors.lastname: Weinmann
authors.forename: Julien
authors.initials: J
authors.lastname: Gaudias
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Bachmann
authors.forename: Serge N
authors.initials: SN
authors.lastname: Schiffmann
authors.forename: Kaspar E
authors.initials: KE
authors.lastname: Vogt
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D055724:Electrophysiological Phenomena; D058851:GPI-Linked Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011689:Purkinje Cells / Q000502:physiology / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse