BRAIN Initiative Unlocks the Secrets of Brain Complexity

A group of international scientists has achieved a significant milestone by mapping the genetic, cellular, and structural composition of both the human brain and the brain of nonhuman primates. This groundbreaking achievement, made possible through funding from the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, known as The BRAIN Initiative®, provides a deeper understanding of the cellular basis of brain function and dysfunction.

This knowledge has the potential to open new avenues for developing precise therapeutics for individuals with mental disorders and other brain-related conditions. These findings have been published in a collection of 24 papers across reputable scientific journals, including Science, Science Advances, and Science Translational Medicine. 

“Mapping the brain’s cellular landscape is a critical step toward understanding how this vital organ works in health and disease,” stated Dr. Joshua A. Gordon, Director of the National Institute of Mental Health. These new detailed cell atlases of the human brain and the nonhuman primate brain offer a foundation for designing new therapies that can target the specific brain cells and circuits involved in brain disorders. 

The 24 papers in this comprehensive collection are part of the latest BRAIN Initiative Cell Census Network (BICCN). They provide intricate insights into the remarkably complex diversity of cells within the human brain and the nonhuman primate brain. The studies uncover both similarities and differences in how cells are structured and how genes are regulated in these two brain types. For example: 

Three of the papers present the very first atlas of cells in the adult human brain, meticulously mapping the transcriptional and epigenomic landscape of the brain. The transcriptome represents the complete set of gene readouts in a cell, containing instructions for producing proteins and other cellular products. The epigenome refers to chemical modifications to a cell’s DNA and chromosomes that influence how the cell’s genetic information is expressed. 

Another paper in the collection compares the cellular and molecular properties of the human brain with several nonhuman primate brains, including those of chimpanzees, gorillas, macaques, and marmosets. This analysis reveals clear similarities in the types, proportions, and spatial organization of cells in the cerebral cortex of humans and nonhuman primates.

Moreover, the study suggests that relatively small changes in gene expression within the human lineage have led to alterations in neuronal wiring and synaptic function, potentially contributing to the human brain’s remarkable adaptability, learning capacity, and ability to change. An investigation into how cells differ across various brain regions in marmosets uncovers a connection between the properties of cells in the adult brain and the characteristics of these cells during development.

This link implies that developmental programming is embedded in cells when they are initially formed and is maintained into adulthood. Consequently, certain observable cellular properties in adults may originate early in life. This discovery promises to provide new insights into brain development and function across an individual’s lifespan. 

An exploration of the anatomy and physiology of neurons in the outermost layer of the neocortex, a brain region responsible for higher-order functions such as cognition, motor commands, and language, reveals discrepancies between the human brain and the mouse brain. These differences suggest that this region may be an evolutionary hotspot, with human-specific changes reflecting the higher demands of regulating more complex brain circuits. 

The primary objective of the BICCN is to comprehensively catalog the various cell types in the brain, including their locations, developmental processes, interactions, and regulatory mechanisms. This endeavor aims to enhance our understanding of how brain disorders originate, progress, and can be effectively treated. 

John Ngai, Ph.D., Director of the NIH BRAIN Initiative, praised these studies as a “landmark achievement in illuminating the complexity of the human brain at the cellular level.” He also highlighted the remarkable progress made possible through scientific collaborations formed within the BICCN, suggesting that the field of neuroscience is advancing at an astonishing pace. 

The comprehensive census of brain cell types in both the human and nonhuman primate brains, as presented in this collection of papers, represents a pivotal step toward developing the brain treatments of the future.

These findings have laid the foundation for the BRAIN Initiative Cell Atlas Network, a transformative project that, in conjunction with two other large-scale initiatives—the BRAIN Initiative Connectivity Across Scales and the Armamentarium for Precision Brain Cell Access—aims to revolutionize neuroscience research.

By illuminating the fundamental principles governing the circuit basis of behavior and informing innovative approaches to treating human brain disorders, these projects hold the potential to shape the future of neuroscience and the development of therapies for neurological conditions. 

Reference  

National institute of Health (NIH), “Scientists unveil detailed cell maps of the human brain and the nonhuman primate brain” https://www.nih.gov/news-events/news-releases/scientists-unveil-detailed-cell-maps-human-brain-nonhuman-primate-brain.