Abstract:
Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. We developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex. Applications for brain evolution, neurodevelopmental disorders, aging and space applications will be discussed.

Bio:
Dr. Muotri is a professor at the Departments of Pediatrics and Cellular & Molecular Medicine at UC San Diego. He is also the Director of the Sanford Stem Cell Education and Integrated Space Stem Cell Orbital Research (ISSCOR), the Director of the Archealization Center (ArchC), and Associate Director for the Center for Academic Research & Training in Antropogeny (CARTA). Dr. Muotri earned a BSc in Biological Sciences from the State University of Campinas in 1995 and a Ph.D. in Genetics in 2001 from the University of Sao Paulo, Brazil. He moved to the Salk Institute as Pew Latin America Fellow in 2002 for postdoctoral training in the fields of neuroscience and stem cell biology. His research focuses on brain evolution and modeling neurological diseases using human induced pluripotent stem cells and brain organoids. He has received several awards, including the prestigious NIH Director’s New Innovator Award, NARSAD, Emerald Foundation Young Investigator Award, Surugadai Award, Rock Star of Innovation, NIH EUREKA Award, two Telly Awards for Excellence in Science Communication, among several others.