Long-term potentiation and inhibition induced by human induced pluripotent stem cell-derived cortical neurons (hiPSC-NC)

Induction of long-term potentiation and depression phenomena in human induced pluripotent stem cell-derived cortical neurons.

A. Odawara, H. Katoh, N. Matsuda, I. Suzuki
Volume 469, Issue 4, 22 January 2016, Pages 856–862

Highlights
• HFS induced LTP and LTD phenomena in hiPSC-derived cortical neurons.
Spike patterns were generated or disappeared from induction of plasticity.
•hiPSC-derived neurons express the spike pattern with a precise timing change.
• HFS induced L-LTP-like plasticity and the change of synchronized burst firing.
• MEA system is beneficial for clarifying the function of hiPSC-derived neurons.

Abstract
Plasticity such as long-term potentiation (LTP) and long-term potentiation depression (LTD) in neuronal networks has been analyzed using in vitro and in vivo techniques in simple animals to understand learning, memory, and development in brain function. Human induced pluripotent The stem cell (hiPSC)-derived neurons may be used by understanding the plasticity mechanism in human neuronal networks, such elucidating disease mechanisms and drug discoveries. In this study, we attempted the induction of LTP and LTD phenomena in a cultured hiPSC-derived cerebral Cortical neuronal network using multi-electrode array (MEA) systems. High-frequency stimulation (HFS) produced a potentiated and depressed transmission in a neuronal circuit for 1 h in the evoked responses by test stimulus. The cross-correlation of responses revealed that spike Patterns with specific timing were generated during LITU induction and disappeared during LTD induction and during the hiPSC-derived cortical neuronal Network has the potential to repeatedly express the spike pattern with a precise timing change within 0.5 ms. We also detected the phenomenon for late-phase LTP (L-LTP) like plasticity and the effects for synchronized burst firing (SBF) in spontaneous firings by Hf. In conclusion, we detected the LTP and LTD phenomena in a hiPSC-derived neuronal network as the change of spike pattern. The studies of plasticity using hiPSC-derived neurons and a MEA system may be beneficial for clarifying the functions of human neuronal circuits And for applying to drug screening.

The mechanisms of neural plasticity such as long-term potentiation (LTP) and long-term potentiation inhibition (LTD) in neural networks, and various brain functions related to learning, memory, and development have been developed through different animal models, using ex vivo and vectors. And other techniques to analyze the research. Human induced pluripotent stem cell-derived neurons (hiPSC-NC) can be effectively used to understand the plasticity mechanisms of human neural networks, thereby elucidating disease pathogenesis and aiding drug development. In this study, researchers at the Tohoku University of Technology in Japan attempted to induce LTP and LTD in cultured hiPSC cortical neurons using a multi-electrode array (MEA) system. High frequency stimulation (HFS) produces a set of evoked responses for up to one hour of synergy and inhibition in neuronal circuits. Corresponding corresponding reactions showed that the peak potential pattern with special time value was generated in the induction of LTP and disappeared in LTD induction, and it is possible for the hiPSC-derived cortical neuron network to repeatedly express the peak potential with time accuracy. Within 0.5 ms. The researchers also detected late plasticity-like LTP phenomena (L-LTP) and synchronous cluster-like emission (SBF) in self-powered emission similar to HFS. The researchers observed that the LTP and LTD phenomena in the hiPSC-derived neuronal network were accompanied by changes in the peak potential pattern. The use of hiPSC-derived neurons and MEA systems can help researchers study the function of human neuronal circuits and the plasticity of drug screening.