Incredibly detailed cell maps help pave the way for a new generation of treatments. An international team of scientists has mapped the genetic, cellular and structural makeup of the human brain and the brains of non-human primates. Through funding from the National Institutes of Health's Brain Research Advancing Innovative Neurotechnologies Program, scientists are gaining a deeper understanding of brain structure, resulting in a deeper understanding of the cellular basis of brain function and dysfunction, paving the way for a new generation of precision therapies for patients with mental disorders and other brain diseases.
Researchers have mapped the genetic and cellular makeup of human and non-human primate brains, providing the possibility to gain insights into brain function and treat disease. This research is part of the BRAIN Initiative, which has published a total of 24 papers and is expected to make transformative progress in the field of neuroscience.
These research results were published in 24 collections of papers in the magazines "Science", "Science Advances" and "Science Translational Medicine".
"Mapping the brain's cells is a critical step in understanding how this important organ works in health and disease," said Joshua A. Gordon, MD, director of the National Institute of Mental Health. "These new detailed cellular atlases of the human and non-human primate brains provide the basis for designing new treatments that target specific brain cells and brain circuits involved in brain diseases."
Key findings and insights
In this latest collection of BRAIN Initiative Cell Census Network (BICCN) papers, 24 papers describe in detail the unusually complex diversity of brain cells in the human brain and non-human primates. These studies uncovered similarities and differences in the way cells are organized and genes are regulated in the human and non-human primate brains. For example, three papers in the collection proposed for the first time a cellular atlas of the adult human brain and mapped the brain's transcription and epigenome. The transcriptome is the complete collection of gene readouts in a cell that contains the instructions for making proteins and other cellular products. The epigenome refers to the chemical modifications of a cell's DNA and chromosomes that change how the cell's genetic information is expressed.
In another paper, a comparison of the cellular and molecular properties of the human brain and that of several nonhuman primates (chimpanzees, gorillas, macaques, and marmosets) revealed clear similarities in the types, proportions, and spatial organization of cortical cells in humans and nonhuman primates. Studies of gene expression in cerebral cortical cells across different species suggest that relatively small changes in gene expression across human lineages lead to changes in neuronal wiring and synaptic function that may make the human brain more plastic, supporting the human brain's ability to adapt, learn and change.
A study exploring how cells change in different brain regions of marmosets has found a link between the properties of cells in the adult brain and the properties of those cells during development. This connection suggests that developmental programs are embedded in cells as they form and are maintained into adulthood, and that some of the cellular properties observable in adulthood may originate early in life. The discovery may lead to new insights into brain development and function across the lifespan.
Exploration of the anatomy and physiology of neurons in the outermost layer of the neocortex has revealed differences between human and mouse brains, suggesting that this region may be an evolutionary hotspot, with changes in humans reflecting higher requirements for regulating more complex brain circuits in humans.
BICCN is a pioneering effort to understand the cellular makeup of the brain. Its core goal is to build a comprehensive inventory of brain cells - where they are, how they develop, how they work together and how they regulate their activity - to better understand how brain diseases develop, progress and are best treated.
"This series of studies is a landmark achievement in revealing the complexity of the human brain at the cellular level," said Dr. John Ngai, director of the NIH Brain Program. "The scientific collaborations forged through BICCN are driving this field forward at an exponential rate; the progress and possibilities are simply breathtaking."
The census of brain cell types in the human and nonhuman primate brains focused on in this paper is a critical step toward developing future brain treatments. These findings also laid the foundation for the BRAIN Initiative Cell Atlas Network. The BRAIN Initiative Cell Atlas Network is a transformative project that joins two other large-scale projects - the BRAIN Initiative Connectivity Across Scales and the Armamentarium for Precision Brain Cell Access - that aim to revolutionize neuroscience research by elucidating the fundamental principles underlying the circuits that govern behavior and inform new approaches to treating human brain diseases.