Summary: A new map of the human brain reveals cells, receptors, and gene activity change along the same boundaries.
Source: Human Brain Project
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 organisation.
The HBP researchers conducted a study that targeted three levels of cortical organisation: cytoarchitecture, neurotransmitter receptor architecture and neurotransmitter receptor gene expression.
The study elucidates principles of human brain organisation 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 analysed 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 organisation 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 analysed differential gene expression within brain areas of each of those functional systems.
“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 organisation.
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 pathogenesis of brain disorders with alterations in neurotransmitter systems.
Combined analysis of cytoarchitectonic, molecular and transcriptomic patterns reveal differences in brain organization across human functional brain systems
Brain areas show specific cellular, molecular, and gene expression patterns that are linked to function, but their precise relationships are largely unknown.
To unravel these structure-function relationships, a combined analysis of 53 neurotransmitter receptor genes, receptor densities of six transmitter systems and cytoarchitectonic data of the auditory, somatosensory, visual, motor systems was conducted.
Besides covariation of areal gene expression with receptor density, the study reveals specific gene expression patterns in functional systems, which are most prominent for the inhibitory GABAA and excitatory glutamatergic NMDA receptors.
Furthermore, gene expression-receptor relationships changed in a systematic manner according to information flow from primary to higher associative areas.
The findings shed new light on the relationship of anatomical, functional, and molecular and transcriptomic principles of cortical segregation towards a more comprehensive understanding of human brain organization.