On November 12, international neuroscientists published a detailed three-dimensional cellular atlas of the human basal ganglia in a collection of nearly 30 studies in the journal Cell.
These deep-brain structures, roughly the size of two grapes, control movement, decision-making, habit formation, and emotional regulation. Their dysfunction contributes to neurological and psychiatric disorders such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, addiction, obsessive-compulsive disorder, bipolar disorder, and schizophrenia.
The mapping effort forms part of the BRAIN Initiative Cell Atlas Network (BICAN), a project comparable in scope to the Human Genome Project. Researchers analyzed 25.5 million individual cells from brain tissue, including 21 million human cells, 3 million macaque cells, and 1.5 million common marmoset cells. By comparing these species, scientists identified 61 shared cell types preserved across more than 76 million years of primate evolution.
“A diagnosis of schizophrenia or bipolar disorder remains a devastating life sentence; people with neurodegenerative diseases also suffer enormously and, unfortunately, die prematurely from them.” said Evan Macosko, associate professor of psychiatry and neurobiology at Harvard Medical School and co-author of the new map.
Rare Neurons Linked to Schizophrenia Risk
Within the striatum, a primary input structure of the basal ganglia, investigators identified a rare type of nerve cell that expresses a unique combination of genes encoding receptors for dopamine and serotonin, two neurotransmitters long associated with psychiatric conditions. Researchers discovered a rare type of neuron called STR D2 SMYD2-HTR7, located in the striatum, that exhibits a variation linked to the genetic risk of schizophrenia.
When Nelson Johansen, a neuroscientist at the Allen Institute, and his team compared these cellular profiles with genetic studies on psychiatric disorders, they discovered that the genetic risk for schizophrenia concentrates within this specific nerve population.
Despite this concentration of genetic risk, researchers emphasize that the discovery does not prove these neurons directly cause schizophrenia. Future studies must determine whether their activity differs in patients with the condition and how they interact with neighboring brain circuits.
Bridging Gap Between Animal Models and Humans
The multi-species approach allowed researchers to bridge the gap between animal models and human neurobiology. Common marmosets proved particularly valuable because their small brains, weighing about 8 grams, allow for complete mapping while still sharing a recent common ancestor with humans. This cross-species integration helped test algorithms capable of handling millions of cells across different primates.
Additional analyses within the published collection revealed that cell proportions in the striatum vary considerably among individuals. Another study examining approximately 4 million cells from 178 donors aged 27 to over 90 found that certain neuronal and glial groups decrease with age, and gene expression patterns can predict a person’s chronological age.
“We are at a point where, for the first time, we have technology and tools capable of answering questions about the nervous system that have gone unanswered for decades.” noted researchers.
Frequently Asked Questions About the Brain Atlas
How many species were included in the basal ganglia mapping project?
The international consortium studied 25.5 million individual cells sourced from humans, rhesus and cynomolgus macaques, and common marmosets.
What specific brain region does the new atlas cover?
The research focuses on the basal ganglia, a group of interconnected structures deep within the brain that regulate movement, emotion, and decision-making.
Does finding this rare neuron mean a cure for schizophrenia is imminent?
No. While the atlas links genetic risk for schizophrenia to the neuron type, researchers note that extensive follow-up studies are required to understand how these cells function in disease states before any treatments can be developed.