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Preclinical Core

Director: Sheryl S. Moy, Ph.D
Co-Director: William D. Snider, M.D.

The Preclinical Core provides IDDRC investigators with multiple approaches for research in animal models, with an overall goal of linking abnormal behavioral phenotypes to changes in brain structure, regional connectivity, cellular function and molecular processes. The Core has three components: the Mouse Behavioral Phenotyping Laboratory, the Confocal and Multiphoton Imaging Facility, and the Brain Imaging Analysis Service. By spanning multiple aspects of mouse model evaluation and use, these components provide a basis for integrative, translational neuroscience within the UNC IDDRC.

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The Mouse Behavioral Phenotyping Laboratory provides testing services, training, and access to an extensive set of automated measurement systems and other equipment for behavioral evaluation. Procedures have been selected to provide an optimal screen for detecting differences across a wide range of functioning – motoric, sensory, emotional, cognitive, and social. The Laboratory typically uses a global assessment approach to determine phenotypic profiles of both behavioral deficits and sparing, which can then be compared to clinical profiles of human disorders. In particular, the Laboratory has standardized specific batteries for the identification of social deficits, repetitive behavior, and other abnormal phenotypes related to developmental disabilities, and for the utilization of behavioral mouse models as preclinical screens for drug discovery initiatives. Laboratory personnel also have extensive expertise in methodology for preclinical drug studies, including initial tests for appropriate dosing and side-effects and the use of implanted minipumps or pellets for chronic drug regimens.

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Image from Eva Anton, IDDRC investigator

The Confocal and Multiphoton Imaging Facility supports studies on cellular and molecular mechanisms in neurodevelopment, utilizing labeled neural tissue, brain slices, or intact, living embryonic brains. The facility provides a full spectrum of advanced systems for cellular and molecular imaging of in vitro and in vivo samples. Resources include a latest-generation confocal Zeiss LSM 710, acquired in 2010, with high photon collection efficiency, diffraction grating-based spectral separation, capable of imaging the full spectra of all the labels available on the market, and automation software, allowing acquisition of 3D mosaic images from whole brain slices. The Facility also offers access to a Zeiss LSM 7 MP dedicated multiphoton microscopy system, installed in March 2011, for in vivo brain imaging of adult mice and embryos, with maximized emission photon collection. The LSM 7MP is equipped with the most sensitive gallium arsenide phosphide detectors for deep brain imaging. In addition, the microscopy facility has recently obtained an LD Apochromat 20x/1.0 Scale, a special lens for visualization of cleared tissue specimens. This new lens will allow imaging of individual cells from depths of up to 6 mm.

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Brain Imaging Analysis Service processes data from magnetic resonance (MRI) and diffusion tensor (DTI) imaging within a state-of-the-art computational facility and UNIX client-server environment. The laboratory maintains the major packages for brain image processing, but also hosts a dashboard with regression testing of its own development of image processing tools, with 5 workstations dedicated to rodent MRI analysis. While the Core does not generate rodent scans, resources to conduct rodent imaging are available through the UNC Biomedical Research Imaging Center (BRIC). The Brain Imaging laboratory has developed a number of semi-automated analysis workflows for rat and mouse brain MRI scans at multiple developmental time points. The table below lists the core measurements and assessment from structural MRI (sMRI, T1 weighted and T2 weighted imagery) and diffusion tensor imaging MRI (DTI) for mouse and rat brain analysis. All measurements are available for ages PND 5, 14, 24, 40, 80.

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For more information on this service, please contact Martin Styner, Co-Director of the Brain Measurement Laboratory of the IDDRC Clinical Translational Core.

Martin Styner, Ph.D.
Phone: (919) 843-1092
Email: styner@cs.unc.edu

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