The Human Brain Project Study offers insight into the organization of neuroreceptors

A major challenge in neuroscience is understanding how the brain can adapt to a changing world, even with a relatively static anatomy. The way brain areas are structurally and functionally related to one another – their connectivity – is a key component. To explain its dynamics and function, we also need to add another piece of the puzzle: receptors. Now, a new mapping by Human Brain Project (HBP) researchers from Forschungszentrum Jülich (Germany) and Heinrich-Heine-University Düsseldorf (Germany), in collaboration with scientists from the University of Bristol (UK), New York University (USA), Child Mind Institute (USA), and the University of Paris Cité (France) are making advances in our understanding of the distribution of receptors throughout the brain.

The findings were published in Natural Neuroscienceand the data is now freely available to the neuroscientific community through HBP’s EBRAINS infrastructure.

The HBP team used autoradiography to analyze the density of neurotransmitter receptors in very thin films in vitro part of the brain. They measured the density of 14 types of neurotransmitter receptors in 109 areas of the monkey cortex and these data were integrated with several structural parameters into a neuroimaging template.

Neurotransmitter receptors

Receptors are key molecules in signal transmission in the brain. In the neurons, the transmission of information occurs via electrical signals along the axons. But the transfer of information between neurons usually require the release of molecules called neurotransmitters into the extracellular space and their binding to receptors on the target neuron.

HBP researchers have found primary and secondary gradients of receptor expression per neuron. In other words, they mapped receptor densities across the cortex and were able to identify two key arrangements, highlighting the connections between the molecular organization and neurons in the cortex. “These two main axes of receptor organization in the ape cortex align with two distinct functional systems, namely the sensory cognition network and the external-internal cognition network. This is the first time such a relationship has been described,” explained Nicola Palomero-Gallagher, researcher at Forschungszentrum Jülich and senior author of the paper.

Integrate maps

In their study, the researchers integrated new neurotransmitter receptor data with multiple layers of anatomical and functional data into a common cortical space within the cortical surface of Yerkes19, a frequently used non-human primate template. Several studies so far have been integrated in vitro anatomy and life ape brain imaging. Creating open-access cortex-wide receptor expression maps that integrate neuroimaging data, as the HBP team did, could accelerate translation across species.

“These are freely available to the neuroscientific community so they can be used by other computational neuroscientists who aim to create other models of biological information,” said Palomero-Gallagher. Part of the data generated for this study has been implemented in a computational model of how dopamine gate information into the frontoparietal working memory network.

Text by Helen Mendes