A high-resolution in vivo atlas of the human brain's benzodiazepine binding site of GABAA receptors
Martin Nørgaard,
Vincent Beliveau,
Melanie Ganz,
Claus Svarer,
Lars H Pinborg,
Sune H Keller,
Peter S Jensen,
Douglas N. Greve,
Gitte M. Knudsen
Affiliations
Martin Nørgaard
Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Rigshospitalet, 2100, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, 2100, Denmark
Vincent Beliveau
Medical University of Innsbruck, Department of Neurology, Innsbruck, 6020, Austria
Melanie Ganz
Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Rigshospitalet, 2100, Denmark; University of Copenhagen, Department of Computer Science, Copenhagen, 2100, Denmark
Claus Svarer
Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Rigshospitalet, 2100, Denmark
Lars H Pinborg
Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Rigshospitalet, 2100, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, 2100, Denmark
Sune H Keller
Department of Clinical Physiology, Nuclear Medicine and PET, Righospitalet, Copenhagen, 2100, Denmark
Peter S Jensen
Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Rigshospitalet, 2100, Denmark
Douglas N. Greve
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, United States
Gitte M. Knudsen
Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Rigshospitalet, 2100, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, 2100, Denmark; Corresponding author.
Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mechanisms of the GABA system, however, no studies have currently combined the techniques to create a high-resolution multimodal view of the GABA system.Here, we present a quantitative high-resolution in vivo atlas of the human brain benzodiazepine receptor sites (BZR) located on postsynaptic ionotropic GABAA receptors (GABAARs), generated on the basis of in vivo [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on ex vivo autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association between BZR protein density and ex vivo mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein.This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain.
