The University of California San Diego School of Medicine researchers have made progress in learning about the development of the cerebral cortex by tracking the ancestry of certain brain cells. Led by Changuk Chung, Ph.D., and Xiaoxu Yang, Ph.D., the study provides new insights into the growth of the human forebrain. This research, conducted in the laboratory of Joseph G. Gleeson, M.D., at the School of Medicine Department of Neurosciences and the Rady Children’s Institute for Genomic Medicine, enhances our knowledge of how the human brain matures.
The research delves into the operations at the cellular level.
The study also provides proof for the existence of inhibitory neurons (dInNs) in the human brain that have different origins compared to other species such as mice, which are commonly used in brain studies. The group detailed their findings in a recently published paper in the journal Nature.
The forebrain, also known as the cerebral cortex, is the largest part of the brain and is crucial for various functions, including cognitive thought, vision, attention, and memory. Neurons, which are cells that act as the individual circuits of the brain, play a significant role in these functions. Inhibitory neurons typically operate as a type of neural “off” switch.
The switch for inhibitory neurons is different from the “on” switch for excitatory neurons.
According to Gleeson, humans have a large and folded cortex that likely helps with higher cognitive functions compared to rodents.
He mentioned that inhibitory neurons in mice originate deep within the developing brain. The current study tests this model by examining cellular lineage. They discovered the existence of dInNs, which are not present in mice. Finding evidence of this specific type of neuron in humans opens up possibilities for better understanding the unique qualities of the human brain.
“We anticipate that dInNs will contribute to new, more accurate”The researcher, Gleeson, stated that the updated brain model could provide insight into the origins of conditions such as epilepsy, schizophrenia, and autism. The group focused on tracking the lineage of mosaic variants of brain cells, where cells with the same mother cell are considered to have the same lineage. Yang explained that if two individual cells have the same mosaic variant, they were born from a common mother cell, functioning like family names in people.The researchers obtained brains from two neurotypical donors who died naturally and used mosaic variants to track the origin of cells, identify sister cells from the same brain region, and determine the spread of each “family name” across the brain.
They discovered that some inhibitory and excitatory neurons share the same family name, indicating a shared lineage. This suggests that the two types of neurons likely branched off during late embryonic cerebral development, a relationship not found in other species, according to Chung.
“We hope our paper will assist other researchers in their work.”Researchers at the University of California San Diego, including Changuk Chung, Xiaoxu Yang, Joseph G. Gleeson, Robert F. Hevner, Keng Ioi Vong, Yang Liu, and Arzoo Patel, are working to develop improved models of neurological disease. By studying impaired brain development, they aim to understand which types of brain diseases can result from these issues. Gleeson emphasized the importance of this research for advancing our knowledge of neurological conditions.Rahul Nedunuri, Scott T. Barton, Geoffroy Noel, Chelsea Barrows, Valentina Stanley, Swapnil Mittal, and Johannes C.M. Schlachetzki from the School of Medicine Department of Neurosciences, and Rady Institute, along with other co-authors Stephen F. Kingsmore and Rady Chi.Children’s Institute for Genomic Medicine; Katie Kennedy from BioSkryb Genomics Inc.; and Martin W. Breuss from the Department of Pediatrics, Section of Clinical Genetics and Metabolism at the University of Colorado Aurora.
This study received support from the National Institute of Mental Health (NIMH) grants U01MH108898, R01MH124890, and R21MH134401; a grant from the Larry L. Hillblom Foundation; a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) K99HD111686; a 2021 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation; and the Rady Children’s Institute for Genomic Medicine.
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