Justine Hansen, Montreal Neurological Institute
Hansen, J. Y., Shafiei, G., Markello, R. D., Smart, K., Cox, S. M., Nørgaard, M., Beliveau, V., Wu, Y., Gallezot, J., Aumont, E., Servaes, S., Scala, S. G., DuBois, J. M., Wainsten, G., Bezgin, G., Funck, T., Schmitz, T. W., Spreng, R. N., Galovic, M., Koepp, M. J., Duncan, J. S., Coles, J. P., Fryer, T. D., Aigbirhio, F. I., McGinnity, C. J., Hammers, A., Soucy, J., Baillet, S, Guimond, S., Hietala, J., Bedard, M., Leyton, M., Kobayashi, E., Rosa-Neto, P., Ganz, M., Knudsen, G. M., Palomero-Gallagher, N., Shine, J. M., Carson, R. E., Tuominen, L., Dagher, A., & Misic, B. (2022). Mapping neurotransmitter systems to the structural and functional organization of the human neocortex. Nature Neuroscience, 25(11), 1569-1581.
The role of neurotransmitter receptors in the structure and function of the human brain
Neurons in the brain transmit signals to other cells through the release of molecules called neurotransmitters which bind to specific receptors. These receptors effectively mediate the transfer and propagation of electrical impulse from neuron to neuron, which is how brain cells communicate. A new study led by Justine Hansen at McGill University used advanced computational approaches to collate data from brain scans (Positive Emission Tomography, or PET) from more than 1,200 healthy individuals to construct a whole-brain 3D atlas of 19 receptors and transporters across nine different neurotransmitter systems. This impressive endeavour shows the map of receptors is a key layer in the multiscale organization of the brain, and reveals how the chemical signals (neurotransmitters) help shape brain architecture and function.
Indeed, the researchers found a strong link between neurotransmitter receptor distribution and both brain structure and function, which highlights the important role of neurotransmitters in shaping the brain. Using diffusion-weighted MRI and fMRI, they show that neurotransmitter receptors densities follow the organizational principles of the brain’s structural and functional connectomes. Moreover, they find that neurotransmitter receptor densities shape magnetoencephalography (MEG)-derived oscillatory neural dynamics.
To determine how neurotransmitter receptor distributions affect cognition and disease, they analysed receptor distributions across 13 neurological, psychiatric, and neurodevelopmental disorders (for N=21,000 patients against N=26,000 controls), uncovering specific receptor-disorder links. They validated these findings and extended the scope of the investigation to additional receptors using an independently collected receptor dataset. Altogether, this study used data from multiple experimental methods, across a range of scales to build a robust characterization of how neurotransmitter receptors shape brain structure and function in both health and disease.
This work also maps receptors to disease-specific structural changes across a wide range of disorders. A key step toward developing therapies for specific syndromes is to reliably map them onto underlying neural systems. This goal is challenging because psychiatric and neurological classification is built around clinical features, rather than neurobiological mechanisms. These results complement some previously established associations between disorders and neurotransmitter systems, and reveal new associations, which will help to identify novel targets for pharmacotherapy.
The data generated in this study has been made available publicly as part of a large and international open science effort to map the human brain, to better understand how it works. The comprehensive approach of this study showcases novel associations that may not have been considered before. This large-scale characterization of receptor systems will hopefully inspire future studies, driving the cycle of discovery. Altogether, these data and analyses provide a framework for testing predictions from the wider literature and consolidating knowledge about neurotransmitter systems.
About Justine Hansen
Justine Hansen performed this study as a PhD student in the Network Neuroscience Laboratory, led by Dr. Bratislav Misic at the Montreal Neurological Institute. She is interested in how neurotransmitter receptors shape brain structure and function but at the time there was no comprehensive multi-receptor dataset. Justine Hansen and Dr. Misic therefore began reaching out to researchers who study neurotransmitter receptor systems to collate data across multiple sites and individuals. This effort began locally (e.g. McGill University, Universite de Quebec a Montreal), spread to other provinces (e.g. Western University, University of Ottawa), across the American border (Yale University), and finally across the ocean (Te.g. urku University Hospital, University of Cambridge, King’s College London). Justine led this data sharing collaboration that resulted in an open-source multi-receptor human atlas of receptor distributions. She then mapped receptors to brain structure, function, dynamics, cognition, and disease. Altogether, with the support from her supervisor and collaborators, Justine Hansen spearheaded a comprehensive characterization of how receptor systems fit in with the rest of the brain.
Sources of funding
Natural Sciences and Engineering Research Council of Canada (NSERC)
Fonds de reserches de Quebec (FRQ-NT)
Helmholtz International BigBrain Analytics & Learning Laboratory (HIBALL)