Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation

Abstract The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical c...

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Main Authors: Rongkang Deng, Joseph P. Y. Kao, Patrick O. Kanold
Format: Article
Language:English
Published: Nature Portfolio 2021-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-82679-2
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author Rongkang Deng
Joseph P. Y. Kao
Patrick O. Kanold
author_facet Rongkang Deng
Joseph P. Y. Kao
Patrick O. Kanold
author_sort Rongkang Deng
collection DOAJ
description Abstract The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.
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spelling doaj.art-0258e50750d14b5f9393765fc78f8ed32022-12-21T20:34:01ZengNature PortfolioScientific Reports2045-23222021-02-0111111810.1038/s41598-021-82679-2Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleationRongkang Deng0Joseph P. Y. Kao1Patrick O. Kanold2Department of Biology, University of MarylandCenter for Biomedical Engineering and Technology, and Department of Physiology, University of Maryland School of MedicineDepartment of Biomedical Engineering, Johns Hopkins UniversityAbstract The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.https://doi.org/10.1038/s41598-021-82679-2
spellingShingle Rongkang Deng
Joseph P. Y. Kao
Patrick O. Kanold
Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
Scientific Reports
title Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
title_full Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
title_fullStr Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
title_full_unstemmed Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
title_short Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
title_sort aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
url https://doi.org/10.1038/s41598-021-82679-2
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AT josephpykao aberrantdevelopmentofexcitatorycircuitstoinhibitoryneuronsintheprimaryvisualcortexafterneonatalbinocularenucleation
AT patrickokanold aberrantdevelopmentofexcitatorycircuitstoinhibitoryneuronsintheprimaryvisualcortexafterneonatalbinocularenucleation