title: In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons.
abstract: The molecular mechanisms that control how progenitors generate distinct subtypes of neurons, and how undifferentiated neurons acquire their specific identity during corticogenesis, are increasingly understood. However, whether postmitotic neurons can change their identity at late stages of differentiation remains unknown. To study this question, we developed an electrochemical in vivo gene delivery method to rapidly manipulate gene expression specifically in postmitotic neurons. Using this approach, we found that the molecular identity, morphology, physiology and functional input-output connectivity of layer 4 mouse spiny neurons could be specifically reprogrammed during the first postnatal week by ectopic expression of the layer 5B output neuron-specific transcription factor Fezf2. These findings reveal a high degree of plasticity in the identity of postmitotic neocortical neurons and provide a proof of principle for postnatal re-engineering of specific neural microcircuits in vivo.
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
authors.forename: Andres
authors.initials: A
authors.lastname: De la Rossa
authors.forename: Camilla
authors.initials: C
authors.lastname: Bellone
authors.forename: Bruno
authors.initials: B
authors.lastname: Golding
authors.forename: Ilaria
authors.initials: I
authors.lastname: Vitali
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moss
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
authors.forename: Christian
authors.initials: C
authors.lastname: Lüscher
authors.forename: Denis
authors.initials: D
authors.lastname: Jabaudon
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D000075402:Channelrhodopsins; D002772:Cholera Toxin / Q000378:metabolism; D003512:Cyclohexanones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004622:Embryo, Mammalian; D053503:Epithelial Sodium Channels / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D018709:Statistics, Nonparametric; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D000075402:Channelrhodopsins; D003512:Cyclohexanones; D004268:DNA-Binding Proteins; D053503:Epithelial Sodium Channels; D009419:Nerve Tissue Proteins; C507047:Scnn1a protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D049452:Green Fluorescent Proteins; C018031:1,2-cyclohexanedione; D002772:Cholera Toxin