title: Oligophrenin-1 regulates number, morphology and synaptic properties of adult-born inhibitory interneurons in the olfactory bulb.
abstract: Among the X-linked genes associated with intellectual disability, Oligophrenin-1 (OPHN1) encodes for a Rho GTPase-activating protein, a key regulator of several developmental processes, such as dendrite and spine formation and synaptic activity. Inhibitory interneurons play a key role in the development and function of neuronal circuits. Whether a mutation of OPHN1 can affect morphology and synaptic properties of inhibitory interneurons remains poorly understood. To address these open questions, we studied in a well-established mouse model of X-linked intellectual disability, i.e. a line of mice carrying a null mutation of OPHN1, the development and function of adult generated inhibitory interneurons in the olfactory bulb. Combining quantitative morphological analysis and electrophysiological recordings we found that the adult generated inhibitory interneurons were dramatically reduced in number and exhibited a higher proportion of filopodia-like spines, with the consequences on their synaptic function, in OPHN1 ko mice. Furthermore, we found that olfactory behaviour was perturbed in OPHN1 ko mice. Chronic treatment with a Rho kinase inhibitor rescued most of the defects of the newly generated neurons. Altogether, our data indicated that OPHN1 plays a key role in regulating the number, morphology and function of adult-born inhibitory interneurons and contributed to identify potential therapeutic targets.
authors.affiliation: Neuroscience Institute - CNR, Padova, Italy.|VIMM Padova, Italy.
authors.forename: Nelly
authors.initials: N
authors.lastname: Redolfi
authors.affiliation: Neuroscience Institute - CNR, Padova, Italy.|VIMM Padova, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Galla
authors.affiliation: VIMM Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maset
authors.affiliation: Neuroscience Institute, CNR, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Murru
authors.affiliation: VIMM Padova, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Savoia
authors.affiliation: Department of Bioscience, Padova, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zamparo
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy (TIGET) Milano, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Gritti
authors.affiliation: Institute Cochin, Inserm, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Billuart
authors.affiliation: Neuroscience Institute, CNR, Milano, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Passafaro
authors.affiliation: Neuroscience Institute - CNR, Padova, Italy.|VIMM Padova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lodovichi
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003712:Dendrites / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D020690:GTPase-Activating Proteins / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D007395:Interneurons / Q000187:drug effects / Q000473:pathology; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics*; D009830:Olfactory Bulb / Q000187:drug effects / Q000473:pathology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C111952:OPHN1 protein, human; C498439:Ophn1 protein, mouse; D054460:rho-Associated Kinases