NHMRC Senior Principal Research Scientist, NeuRA
Conjoint Scientia Professor of the School of Medical Sciences, UNSW
Prof George Paxinos completed his BA at The University of California at Berkeley, his PhD at McGill University, and spent a postdoctoral year at Yale University. He and Charles Watson are the authors of The Rat Brain in Stereotaxic Coordinates. With over 50,000 citations across its 7 Editions (March 2014), it is the third most cited book in science after Molecular Cloning and the Diagnostic and Statistical Manual of Mental Disorders. Prof Paxinos has also published another 45 books on the structure of the brain of humans and experimental animals, his most recent being MRI/DTI Atlas of the Rat Brain. His work was recognised by an AO, Ramaciotti Medal, Humboldt Prize, a $4 million NHMRC Australia Fellowship and the NSW Premier’s Prize for Excellence in Medical Biological Sciences in 2015. He is a Fellow of the Australian Academy of Science, the Academy of Social Sciences in Australia and a corresponding member of the Academy of Athens. His novel Κατ’ Εικόνα (In His Image) was published in Greek in 2015 (English version pending).
Prof Paxinos’s most significant atlases and books
The Paxinos and Watson Collaboration
Nissl and AChE Staining Protocols for Beginners
The Australian Research Council Centre of Excellence for Integrative Brain Function
Brain Dialogue: MRI/DTI Rat Brain Atlas
Dr Huazheng (Andy) Liang has been investigating the pathways that connect the brain to the spinal cord for the past 9 years. Currently he is researching the termination pattern of projections arising from the subcoeruleus and trigeminal nuclei as well as the chemical characteristics of rubrospinal and vestibulospinal pathways. He is particularly interested in the influence of the monoaminergic systems (eg. serotonergic, dopaminergic, adrenergic and noradrenergic pathways) on the spinal cord. He has recently worked up the CLARITY/CUBIC technique in the NeuRA laboratory, which was developed by Deisseroth and colleagues at Stanford University in 2013 (Chung et al., 2013, Nature). This technique dissolves lipid from brain tissue, rendering it transparent and thereby enabling researchers to investigate the intact mouse brain (traditional microscopic analysis involves cutting, and therefore distorting, the brain tissue). The transparent brain can be imaged in 3D, allowing careful investigation of specific types of neurons and their axonal projections in both the brain and spinal cord.
Prof Paxinos is joining Assoc Prof Pavel Osten at Cold Spring Harbour Laboratory in developing a method to rapidly determine the identity and cell composition of any region within the whole mouse brain using a combination of histological and statistical modelling techniques. By using advanced techniques such as two-photon microscopy* and mechanical tissue sectioning from a block face (which does not distort the tissue with cutting) they will be able to create detailed 3D maps in wild-type and transgenic mice at a resolution of 1μm. This technique is so precise that it can create 5,600 serial coronal sections from a single mouse brain (XY = 1 μm, Z = 2.5 μm) over a period of 9 days. Individual types of neurons (GABAergic for instance) will be mapped throughout these whole brains at different neurodevelopmental stages and in aging, by using fluorescent tagging techniques. Once a pipeline has been established, it will be a powerful tool for researchers for analysing cell composition throughout the brain in wild-type and transgenic mice.
Prof. Paxinos and Dr Schofield have produced very high resolution images of the adult and postnatal day 6 mouse brain at 40 micron intervals in 3 planes of section corresponding to The Mouse Brain in Stereotaxic Coordinates (Paxinos and Franklin, 4th Edition, Academic Press, San Diego, 2013) (Fig 1 and Fig 2). Prof. Susumu Mori and Jaymin Patel, collaborators at John’s Hopkins University, will use a population-based MRI/CT 3D atlas as a master high-anatomical-fidelity atlas to register the serial sections created in the Paxinos laboratory in all three directions. The registration parameters for matching each histology section to the master coordinates was established, and then each histology coordinate was linked to the 3D master atlas based on the labels in The Mouse Brain in Stereotaxic Coordinates (Paxinos et al., 2013). The Mori laboratory is developing a web-based interface (www.mricloud.org) to deploy these rich histological data with about 1,000 sections (each about 1GB) for users to explore the neuroanatomy in a 3D space.
The most recent project completed by Paxinos and Watson was the publication, in book form, of the first of a new generation of atlases exploiting the power of magnetic resonance histology, diffusion tensor imaging and digital atlasing. With the combined experience of Prof. Paxinos and Al Johnson (a Professor of Radiology, Physics, and Biomedical Engineering from Duke University) and support from The ARC Centre of Excellence for Integrative Brain Function based at Monash University, an MRI/DTI atlas of the rat brain was constucted , and the next step is the construction of an equivalent mouse brain atlas that can be used as a reference for researchers working with mice, particularly transgenic mice. Accurate brain atlases are essential to studies using animal models of human brain pathology, such as Parkinson’s disease and Alzheimer’s disease. By far the most widely used animal brain atlas for transgenic mice is the histological atlas of the mouse brain by Paxinos and Franklin. The new MRI/DTI atlas of the mouse brain will be directly compatible with the histological atlas (Paxinos and Franklin 4th Ed., 2013). An accurate MR atlas would have many practical and technical advantages over a histological atlas, including the fact that it can generate 3D images, and can be used with living animals, which can be scanned repeatedly without injury.
In collaboration with MR experts Al Johnson (a Professor of Radiology, Physics, and Biomedical Engineering from Duke University) and Dr Mark Schira at the University of Wollongong, we are constructing an electronic atlas of the human brainstem. The atlas will combine in vivo magnetic resonance imaging, magnetic resonance microscopy, and histological images and be compatible with tablet computers to provide a convenient, yet powerful, reference for research and clinical use. We will also create an anatomical template to be used with most common MR-analysis packages (e.g., SPM, FSL, MINC, and BrainVoyager), to allow fast and effective alignment and warping of new data into the atlas framework.
DR TERI FURLONG Postdoctoral Fellow
DR CHRISTODOULOS SKLIROS PhD Fellow
KEIRA MCCLOSKEY Research Assistant
KATERINA ARVANITAKIS Research Assistant