title: GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex.
abstract: GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain.
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.|Centre for Neuroscience, Imperial College Faculty of Medicine, Hammersmith Hospital, Imperial College London, London W12 0NN, UK.
authors: Paul G
authors: PG
authors: Anastasiades
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors: Andre
authors: http://orcid.org/0000-0001-6879-2858
authors: A
authors: Marques-Smith
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors: Daniel
authors: http://orcid.org/0000-0002-3708-0249
authors: D
authors: Lyngholm
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors: Tom
authors: T
authors: Lickiss
authors: Centre for Neuroscience, Imperial College Faculty of Medicine, Hammersmith Hospital, Imperial College London, London W12 0NN, UK.
authors: Sayda
authors: S
authors: Raffiq
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.|Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors: Dennis
authors: D
authors: Kätzel
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.|Centre for Neural Circuits and Behaviour, University of Oxford, Oxford OX1 3SR, UK.
authors: Gero
authors: G
authors: Miesenböck
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors: Simon J B
authors: SJ
authors: Butt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016000:Cluster Analysis; D059330:GABAergic Neurons; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007395:Interneurons; D051379:Mice; D019579:Neocortex / Q000254:growth & development*; D009415:Nerve Net / Q000254:growth & development*; D009687:Nuclear Proteins; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D025341:Principal Component Analysis; D017966:Pyramidal Cells; D013569:Synapses; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D049452:Green Fluorescent Proteins