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Human Stem Cell-Derived Neurons Repair Circuits and Restore N
For rabies tracing experiments, Cre-dependent TVA and tdTomato with nuclear location signal linked through a 2A peptide AAV expressing Cre-dependent Rabies Glycoprotein (From BrainVTA) were co-injected into the graft site of PD mice 5 months after transplantation.
The viruses used in this article from BrainVTA are in the table below
RV  R01001 RVdG-EGFP
Tracing Helper  PT-0149 AAV2/9-Ef1a-DIO-TVA-2A-NLS-tdTomato
 PT-0023 AAV2/9-Ef1a-DIO-G
Pub Date: 2019-09-22, DOI: 10.1016/j.stem.2020.08.014  Email:
Man Xiong, Yezheng Tao, Qinqin Gao, Ban Feng, Wei Yan, Yingying Zhou, Thomas A. Kotsonis, Tingli Yuan, Zhiwen You, Ziyan Wu, Jiajie Xi, Alexander Haberman, Julia Graham, Jasper Block, Wenhao Zhou, Yuejun Chen, and Su-Chun Zhang
Although cell transplantation can rescue motor defects in Parkinson’s disease (PD) models, whether and how grafts functionally repair damaged neural circuitry in the adult brain is not known. We transplanted hESC-derived midbrain dopamine (mDA) or cortical glutamate neurons into the substantia nigra or striatum of a mouse PD model and found extensive graft integration with host circuitry. Axonal pathfinding toward the dorsal striatum was determined by the identity of the grafted neurons, and anatomical presynaptic inputs were largely dependent on graft location, whereas inhibitory versus excitatory input was dictated by the identity of grafted neurons. hESC-derived mDA neurons display A9 characteristics and restore functionality of the re-constructed nigrostriatal circuit to mediate improvements in motor function. These results indicate similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural networks, highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repair and functional restoration in the adult brain.

Fig.1 Rabies-Mediated Tracing of Inputs and Axonal Projections and Electrophysiological Properties of Genetically Labeled Human mDA Neurons.
To reveal whether and how grafts functionally repair damaged neural circuitry in the adult brain, the researchers applied genetically labeled cell lines strategies and Rabies-mediated tracing system (From BrainVTA) to reconstruct the neural connection formed by transplanted cells and the host. The results revealed cell-type-dependent functional circuit integration by transplanted neurons, highlighting the prospect of using specialized neuronal types from stem cells to repair the neural circuit to treat neurological conditions.

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