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In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons

Moss, Jonathan
Published in Nature neuroscience. 2013, vol. 16, no. 2, p. 193-200
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.
Keywords Age FactorsAnimalsAnimals, NewbornCell Cycle/drug effects/geneticsCholera Toxin/metabolismCyclohexanones/pharmacologyDNA-Binding Proteins/genetics/metabolismDendrites/metabolismEmbryo, MammalianEpithelial Sodium Channels/geneticsGene Expression Regulation, Developmental/drug effects/genetics/physiologyGreen Fluorescent Proteins/geneticsMembrane Potentials/drug effects/geneticsMiceMice, TransgenicMicroscopy, Electron, TransmissionNeocortex/cytology/embryology/growth & developmentNerve Net/physiologyNerve Tissue Proteins/genetics/metabolismNeural Pathways/physiologyNeurons/physiology/ultrastructurePatch-Clamp TechniquesRhodopsin/geneticsStatistics, NonparametricVesicular Glutamate Transport Protein 2/metabolism
PMID: 23292682
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Research group Mécanismes cellulaires de la dépendance et de l'addiction (520)
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DE LA ROSSA, Andrés et al. In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons. In: Nature neuroscience, 2013, vol. 16, n° 2, p. 193-200. doi: 10.1038/nn.3299 https://archive-ouverte.unige.ch/unige:28708

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Deposited on : 2013-06-26

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