A new study by researchers at UC San Diego provides insights that may improve brain function and disease models by characterizing specific inhibitory neurons in the human forebrain, and shows that certain neurons share a common ancestry, which has significant implications for understanding brain diseases.
Researchers have revealed new insights into the development of the human brain
A team of scientists from the San Diego School of Medicine in California conducted a study that provides new insight into how the human frontal head develops.
The research, led by Changuk Chung, PhD, and Xiaoxu Yang, PhD, both from Joseph G. Gleason, MD, in the School of Medicine’s Department of Neuroscience and the Rady Children’s Institute for Genomic Medicine, will provide greater insight into how the human brain develops at the cellular level.
The study provides evidence for a distinct source of neurons (DNN) in the human brain. Species Like rats, a common laboratory animal used in brain studies. The team reported their results in a paper recently published in the journal Nature.
Functionality and importance of the forebrain
The frontal brain, or cerebral cortex, is the largest part of the brain that is important for a variety of functions, from mental thinking, vision, attention, and memory. Neurons are cells that act as the brain’s single circuit. Inhibitory neurons often act as a type of “off” switch for neurons, as opposed to “on” for excitatory neurons.
“Humans have a much larger and more convoluted cortex than other species, such as rodents, which support higher cognitive functions,” Gleason explained.
A trio of researchers (from left) Xiaoxu Yang, Changuk Chung and Joseph G. Gleeson led a study that advanced understanding of the structure of the human brain at the cellular level. All three are affiliated with the Department of Neuroscience at the University of California, San Diego School of Medicine and the Rady Children’s Institute for Genomic Medicine. Credit: UC San Diego Health Sciences
In mice, protective neurons originate in the developing brain, he said. The current study puts that model to the test by evaluating a cell line. They discovered the presence of DNA that is not found in mice. Finding evidence of this type of neuron in humans opens the door to a better understanding of how the human brain is unique, he said.
“We expect DNA to support new, more accurate models of the human brain,” Gleason said. “This improved brain model may help explain the origins of certain conditions such as epilepsy, schizophrenia or autism.”
Cellular lineage and brain structure
The team was particularly interested in tracing the lineage of mosaic variations of brain cells. “If two cells share the same mother cell, we say they have the same lineage,” Chung said.
“If two single cells have the same mosaic variant, they are born from a common mother cell and will pass it on to all of its daughters,” Yang explained. “So mosaic variations in cells act like family names in humans.
The researchers obtained brains directly from two neurotypical donors who had died of natural causes. They used mosaic differences to determine where these cells came from, to identify siblings born in the same brain region, and to determine how widely each “family name” is distributed throughout the brain.
Some inhibitory and excitatory neurons have essentially the same family name, Chung said, meaning the two neurons share a lineage. The two types may be delayed in fetal cerebral development, he added, adding that such cellular communication does not exist in other species.
“We hope that our paper will help other researchers to generate better neurological models, and which brain diseases may be caused by impaired development,” Gleason said.
Reference: “Cell Type-Resolved Mosaicism Reveals Human Forebrain Dynamics” by Changuk Chung, Xiaoxu Yang, Robert F. Heavner, Katie Kennedy, Keng Ayo Wong, Yang Liu, Arzo Patel, Rahul Nedunuri, Scott T. Barton, 1999; Geoffrey Noel, Chelsea Burrows, Valentina Stanley, Swapnil Mittal, Martin W. Brace, John CM Schlachetzky, Stephen F. Kingsmore and Joseph G. Gleason. Nature.
DOI: 10.1038/s41586-024-07292-5
This work was supported by National Institute of Mental Health (NIMH) grants U01MH108898, R01MH124890, and R21MH134401, and Larry L. Hillblom Foundation Grant; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) grant K99HD111686; 2021 NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation; and the Rady Children’s Institute for Genomic Medicine.