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Learning and Memory in Human Stem Cell-derived 3D Brain Organoids
Secondary Supervisor(s): Dr Dan Ma, Professor Rhein Parri
University of Registration: Aston University
BBSRC Research Themes:
Project Outline
How do human brain circuits form during development, adapt to experience and retain information? Learning and memory depend on changes in communication between brain cells, but much of our knowledge comes from animal studies or 2D planar cell cultures. Human induced pluripotent stem cells (iPSCs) can be grown into brain organoids - three-dimensional models containing diverse brain cell types and spontaneously active neural networks. These models offer a new way to study how human circuits develop and change over time.
The project will engineer region-specific organoids representing the cortex and ventral forebrain, then fuse them to create assembloids - integrated 3D models that mimic how different brain regions connect to form neural circuits. Within these models, inhibitory interneurons can migrate and connect with excitatory neurons to form active neural networks, recapitulating human prenatal forebrain development. The student will investigate how the balance between excitation and inhibition influences network stability, flexibility and plasticity - the ability of neural connections to change with experience.
Network development will be followed using high-density multi-electrode arrays, which record electrical activity from many sites, together with calcium imaging to visualise active networks. Optogenetic viral tools and pharmacological methods will be used to modify the activity of selected cell populations, while quantitative and computational analyses will measure firing patterns, synchrony, plasticity and memory-like responses.
The project will reveal fundamental principles of how developing human neural circuits process and retain information, and explore how these principles could inform neuromorphic computing - human brain inspired computing systems. The student will receive interdisciplinary training in human stem cell biology, 3D brain models, high-resolution imaging, viral techniques, electrophysiology and quantitative data analysis.