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Synaptic circuit restoration and functional recovery in the mouse visual cortex after ischemic injury and direct in vivo reprogramming of astrocytes into neurons
Author(s) -
Chubykin Alexander,
Tang Yu,
Wu Qiuyu,
Ryu Esther,
Pei Zifei,
Chen Yuchen,
Chen Gong
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05621
Subject(s) - reprogramming , neuroscience , glial scar , in vivo , astrocyte , gliosis , biology , cell , central nervous system , genetics , microbiology and biotechnology
Ischemic injury caused by stroke is one of the leading causes of severe morbidity and mortality. Neuronal loss, proliferation of reactive astrocytes and the formation of a glial scar represent the three critical problems preventing the functional recovery. Direct reprogramming of astrocytes into neurons in vivo using NeuroD1‐containing AAV virus represents a new promising gene therapy capable of replenishing the neuronal population and reducing gliosis. We have used NeuroD1‐containing AAV virus to convert astrocytes into neurons in the mouse primary visual cortex (V1) following focal ischemic injury. We have demonstrated that this in vivo reprogramming can restore visual evoked potentials (VEPs) and individual neuronal responses impaired after ischemic injury in V1. We have used Channelrhodopsin Assisted Circuit Mapping (CRACM) to demonstrate that this functional restoration is accompanied by the integration of the newly reprogrammed neurons into the visual microcircuit and reestablishment of the specific interlaminar long‐range connections. Our work suggests that in vivo NeuroD1‐based viral therapy can convert reactive astrocytes into neurons and restore visual function lost after local ischemia Support or Funding Information Purdue Research Foundation