Integration of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons into Rat Brain Circuits

Xiling Yin; Ted M Dawson; Valina L Dawson

doi:10.21769/BioProtoc.3746

Integration of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons into Rat Brain Circuits

Bio Protoc. 2020 Sep 5;10(17):e3746. doi: 10.21769/BioProtoc.3746.

Authors

Xiling Yin^{1

2}, Ted M Dawson^{1

2

3

4

5

6}, Valina L Dawson^{1

2

3

7

5

6}

Affiliations

¹ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
² Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
³ Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
⁴ Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
⁵ Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130, USA.
⁶ Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130, USA.
⁷ Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

Human neuron transplantation offers novel opportunities for modeling human neurologic diseases and potentially replacement therapies. However, the complex structure of the human cerebral cortex, which is organized in six layers with tightly interconnected excitatory and inhibitory neuronal networks, presents significant challenges for in vivo transplantation techniques to obtain a balanced, functional and homeostatically stable neuronal network. Here, we present a protocol to introduce human induced pluripotent stem cell (hiPSC)-derived neural progenitors to rat brains. Using this approach, hiPSC-derived neurons structurally integrate into the rat forebrain, exhibit electrophysiological characteristics, including firing, excitatory and inhibitory synaptic activity, and establish neuronal connectivity with the host circuitry.

Keywords: Electrophysiological characteristics; Excitatory and inhibitory neuronal networks; Human neuron transplantation; Neuronal connectivity; hiPSC-derived neurons.