Engineering novel neuronal circuits using HI-PSCS derived neurons and microglia

The inner workings of our brain’s neural network are one of the most impactful yet simultaneously least understood natural phenomena. Previous research suggested that there might be a link to the emerging role of microglia in synaptic remodeling. However, it is still unclear as to what is the role of microglia during the development and refinement of the neuronal circuits in the brain. From previous in vivo studies, we know that microglia mediate the synaptic pruning during neuronal circuit formation, and thus we hypothesized that microglia will remodel the connections within the human cortical neuronal circuit development, resulting in higher synchronicity and stable firing of action potentials for a longer period of time. The presence of micro-glia could also help the neuronal circuits and systems to reach maturation faster. Here, we engineered an in vitro neuronal model to study the role of microglia and how they can modulate electrophysiological behavior in human-induced Pluripotent Stem Cells (hiPSC) derived cortical neuronal network during development. We characterized the cell population and functionality of neurons and microglia in culture and on a microelectrode array (MEA). The Real Time Quantitative Reverse Transcription (qRT-PCR) showed that we differentiated into a mixture of excitatory and inhibitory neurons that belong to the cortex. This was supported by the immunocytochemistry (ICC) of T-Box Brain Transcription Factor 1 (TBR1) a characteristic protein of the cerebral cortex. Importantly, our initial MEA data suggests that the electrical activity of cortical neurons increased when co-cultures were performed in the presence of microglia.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2021

Author dc:creator

• Ramos-Cruz, Karla P.

Contributors dc:contributor

• Bashir, Rashid

• neurons
• microglia
• human stem cells
• micro electrode array

Statement dc:rights

• © Copyright 2020 by Karla P. Ramos-Cruz All rights reserved.

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/110615

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/110615