title: Agrin-signaling is necessary for the integration of newly generated neurons in the adult olfactory bulb.
abstract: In the adult forebrain, new interneurons are continuously generated and integrated into the existing circuitry of the olfactory bulb (OB). In an attempt to identify signals that regulate this synaptic integration process, we found strong expression of agrin in adult generated neuronal precursors that arrive in the olfactory bulb after their generation in the subventricular zone. While the agrin receptor components MuSK and Lrp4 were below detection level in neuron populations that represent synaptic targets for the new interneurons, the alternative receptor α3-Na(+)K(+)-ATPase was strongly expressed in mitral cells. Using a transplantation approach, we demonstrate that agrin-deficient interneuron precursors migrate correctly into the OB. However, in contrast to wild-type neurons, which form synapses and survive for prolonged periods, mutant neurons do not mature and are rapidly eliminated. Using in vivo brain electroporation of the olfactory system, we show that the transmembrane form of agrin alone is sufficient to mediate integration and demonstrate that excess transmembrane agrin increases the number of dendritic spines. Last, we provide in vivo evidence that an interaction between agrin and α3-Na(+)K(+)-ATPase is of functional importance in this system.
authors.affiliation: Aix-Marseille University, IBDML, 13288, Marseille, France, CNRS, UMR7288, 13288 Marseille, France.
authors.forename: Katja
authors.initials: K
authors.lastname: Burk
authors.forename: Angelique
authors.initials: A
authors.lastname: Desoeuvre
authors.forename: Camille
authors.initials: C
authors.lastname: Boutin
authors.forename: Martin A
authors.initials: MA
authors.lastname: Smith
authors.forename: Stephan
authors.initials: S
authors.lastname: Kröger
authors.forename: Andreas
authors.initials: A
authors.lastname: Bosio
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Tiveron
authors.forename: Harold
authors.initials: H
authors.lastname: Cremer
mesh_terms: D000367:Age Factors; D018171:Agrin / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000502:physiology*; D013569:Synapses / Q000235:genetics
chemical_list: D018171:Agrin; D000254:Sodium-Potassium-Exchanging ATPase; C488756:ATP1A3 protein, human