Dataset Information

Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy.

ABSTRACT: Neural circuits underlying brain functions are vulnerable to damage, including ischemic injury, leading to neuronal loss and gliosis. Recent technology of direct conversion of endogenous astrocytes into neurons in situ can simultaneously replenish the neuronal population and reverse the glial scar. However, whether these newly reprogrammed neurons undergo normal development, integrate into the existing neuronal circuit, and acquire functional properties specific for this circuit is not known. We investigated the effect of NeuroD1-mediated in vivo direct reprogramming on visual cortical circuit integration and functional recovery in a mouse model of ischemic injury. After performing electrophysiological extracellular recordings and two-photon calcium imaging of reprogrammed cells in vivo and mapping the synaptic connections formed onto these cells ex vivo, we discovered that NeuroD1 reprogrammed neurons were integrated into the cortical microcircuit and acquired direct visual responses. Furthermore, following visual experience, the reprogrammed neurons demonstrated maturation of orientation selectivity and functional connectivity. Our results show that NeuroD1-reprogrammed neurons can successfully develop and integrate into the visual cortical circuit leading to vision recovery after ischemic injury.

SUBMITTER: Tang Y

PROVIDER: S-EPMC8416524 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy.

Tang Yu Y Wu Qiuyu Q Gao Mang M Ryu Esther E Pei Zifei Z Kissinger Samuel T ST Chen Yuchen Y Rao Abhinav K AK Xiang Zongqin Z Wang Tao T Li Wen W Chen Gong G Chubykin Alexander A AA

Frontiers in cell and developmental biology 20210818

Neural circuits underlying brain functions are vulnerable to damage, including ischemic injury, leading to neuronal loss and gliosis. Recent technology of direct conversion of endogenous astrocytes into neurons <i>in situ</i> can simultaneously replenish the neuronal population and reverse the glial scar. However, whether these newly reprogrammed neurons undergo normal development, integrate into the existing neuronal circuit, and acquire functional properties specific for this circuit is not kn ...[more]

PMID: 34490268

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Project description:ObjectiveTo investigate the effects of mirror neuron theory-based visual feedback therapy (VFT) on restoration of upper limb function of stroke patients and motor-related cortical function using functional magnetic resonance imaging (fMRI).MethodsHemiplegic stroke patients were randomly divided into two groups: a VFT group and a control (CTL) group. Sixteen patients in the VFT group received conventional rehabilitation (CR) and VFT for 8 weeks, while 15 patients in the CTL group received only CR. The Barthel Index (BI) was used to assess the activities of daily living at baseline and the 8th week of the recovery training period. The Fugl-Meyer assessment (FMA) scale, somatosensory evoked potential (SEP), and fMRI were used to evaluate the recovery effect of the training therapies. The latencies and amplitudes of N9 and N20 were measured. Before recovery training, fMRI was performed for all patients in the VFT and CTL groups. In addition, 17 patients (9 in the VFT group and 8 in the CTL group) underwent fMRI for follow-up 2 months after treatment. Qualitative data were analyzed using the χ 2 test. The independent sample t-test was used to compare normally distributed data among different groups, the paired sample t-test was used to compare data between groups, and the non-parametric test was used to comparing data without normal distribution among groups.ResultsThere were no significant differences between the VFT and CTL group in all indexes. However, after 8 weeks of recovery training, these indexes were all significantly improved (P < 0.05). As compared with the CTL group, the FMA scores, BI, and N9/N20 latencies and amplitudes of SEP in the VFT group were significantly improved (P < 0.05). Two months after recovery training, fMRI showed that the degree of activation of the bilateral central anterior gyrus, parietal lobe, and auxiliary motor areas was significantly higher in the VFT group than the CTL group (P < 0.05).ConclusionsVFT based on mirror neuron theory is an effective approach to improve upper extremity motor function and daily activity performance of stroke patients. The therapeutic mechanism promotes motor relearning by activating the mirror neuron system and motor cortex. SEP amplitudes increased only for patients who participated in visual feedback. VFT promotes sensory-motor plasticity and behavioral changes in both the motor and sensory domains.

Dataset Information

Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy.

Publications

Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy.

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