The Human Brain Project’s study linked neurotransmitter receptor patterns and gene expression to brain function, revealing systematic organization changes.
Obviously, the human brain is incredibly complex, with about 100 billion neurons and an estimated 100 trillion connections. Even if you know the major areas of the brain, such as the cerebral cortex, cerebellum, hypothalamus, thalamus, frontal lobe, occipital lobe, temporal lobe, parietal lobe, amygdala, hippocampus, and medulla oblongata, you’re still far from understanding how the brain is organized on a deeper level that includes cellular, molecular, and gene expression patterns and relationships.
Scientists at the Human Brain Project, a large research project with over 500 researchers from 123 institutions, are working to understand the deep complexities of the human brain. With their custom-built research infrastructure, they are advancing neuroscience to the next level.
Specific cellular, molecular, and gene expression patterns in brain areas are linked to function, but their precise relationships remain largely unknown. New findings by scientists at the Human Brain Project (HBP) shed light on these relationships and enable a more comprehensive understanding of human brain organization.
Targeting Three Levels of Cortical Organization
The HBP researchers conducted a study that targeted three levels of cortical organization: cytoarchitecture, neurotransmitter receptor architecture, and neurotransmitter receptor gene expression. The study elucidates principles of human brain organization across the visual, auditory, somatosensory, and motor functional systems, going beyond the simplified view of a ‘mosaic’ of areas forming the neocortex. The results were published in the journal NeuroImage.
To reveal the different properties of functional systems, and how brain areas within a functional system differ with respect to the processing hierarchy — from primary to higher associative, the team analyzed cytoarchitectonic and receptorarchitectonic data of the Julich Brain Atlas – a three-dimensional multimodal atlas of the human brain – and compared the data with transcriptomic data from the Allen Human Brain Atlas.
“Bridging the gaps between different levels of brain organization is one of the biggest challenges in neuroscience today. In the Julich Brain Atlas, we can do it systematically. It integrates the data and is an invaluable tool,” says Daniel Zachlod, first author of the study.
The researchers investigated the relationship of neurotransmitter receptor densities with their corresponding genes in 15 cytoarchitectonic areas of the visual, auditory, somatosensory, and motor systems. They analyzed differential gene expression within brain areas of each of those functional systems.
Systematic Changes in Brain Architecture
“We found that the receptor architecture and gene expression patterns within a functional system change in a systematic way, in correspondence to increasing complexity of information processing,” explains HBP Scientific Director Katrin Amunts, who is last author of the study.
The study demonstrates a method to unravel structure-function relationships by using the multilevel Julich-Brain Atlas to bridge the different scales of brain organization.
Previous studies had already indicated the relevancy of receptor gene expression for the functional differentiation of the brain in rodents, but data on the human brain is much sparser and more fragmented. The authors of the present study argue that it is mandatory to extend such studies to the human brain, in order to better understand the healthy brain, as well as the pathogenesis of brain disorders with alterations in neurotransmitter systems.
Reference: “Combined analysis of cytoarchitectonic, molecular and transcriptomic patterns reveal differences in brain organization across human functional brain systems” by Daniel Zachlod, Sebastian Bludau, Sven Cichon, Nicola Palomero-Gallagher and Katrin Amunts, 19 May 2022, NeuroImage.
DOI: 10.1016/j.neuroimage.2022.119286
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