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Neural Engineering

Neural Engineering - Poster Session E

Poster Z10 - Integrating Microfluidic and Multi-Electrode Array (MEA) Systems for Live Migration of Inhibitory Interneurons and Excitatory Cortical Neurons

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Cortical neurons and medial ganglionic eminence (MGE) interneurons play crucial roles in the circuitry of the brain. Cortical neurons, primarily excitatory neurotransmitters, form the backbone of the cerebral cortex, contributing to sensory processing, motor control, and higher cognitive functions. Morphologically, they typically exhibit a pyramidal shape with extensive dendritic arborization. Cortical projection neurons undergoing phases of radial migration can be visualized by targeting dorsally located cortical progenitors with a construct expressing the Green/Red Fluorescent Protein (RFP/GFP) or other fluorescent proteins, at a specific embryonic stage. In contrast, MGE interneurons, with inhibitory neurotransmitters, arise from the embryonic MGE region and migrate tangentially first and then radially to integrate into cortical circuits. Their morphological diversity includes basket cells and chandelier cells. The migration of both cortical neurons and MGE interneurons is orchestrated by multiple cues including electrical and molecular stimuli. Understanding the interplay between these neuron migration types and morphology at the axon level during developmental stages of organoids is essential for unraveling the complexities of neural circuits underlying cognition and behavior.

Materials and

Methods:  In this application, we developed Brain-Electrotaxis-on-a-Chip (BEC) using human induced pluripotent stem cells (hiPSC) GFP-dorsal (Cortical) and mcherry-ventral (MGE) organoids to study development of neural networks from Day 15 to Day 35 after organoids aggregation. Spatiotemporal live imaging of twenty days and beyond after seeding organoids in BEC platform will model neuron and interneuron migration pattern, directionality, and velocity during neural developmental stages.

Results, Conclusions, and Discussions: Our preliminary results indicate the success in the development of ex-vivo 2D neural circuitry and for real-time migration of hiPSC dorsal-midbrain organoids at axon scale over 24 days of time-lapse. We observed that human dorsal organoids from day 14 to day 23 after aggregation are showing migration of ventral interneurons. After day 23, human dorsal organoids start to grow neurons into the single channels at the BEC platform.
The next step in this process will be the spatiotemporal measurement of dorsal-ventral neurons. Following this, we will disturb migration patterns and development speed using chemicals such as glutamine (excitatory neurotransmitter) and glycine (inhibitory neurotransmitter), along with electrical stimulation ranging from -70mV to +30mV. This platform will model neural development, investigate neurotransmitter effects, and analyze the impact of electrical ionic delivery on neuron migration. The final goal of the BEC platform is to model neurological disorders and perturb neural networks, shedding light on the underlying mechanisms of conditions like ADHD, autism, and other neurodevelopmental disorders.

Acknowledgements (Optional):