Advances in the field of mouse genetics, including truly remarkable new strategies for controlled gene expression and engineering of mutant lines, have significantly enhanced the use of murine models in the study of intellectual and developmental disabilities (IDD). The Preclinical Core (PC) offers innovative, multidisciplinary approaches for measurement at the level of behavior, brain, and cell. These services are essential for IDDRC projects utilizing mouse models in genetic, molecular, neurobiologlcal, and preclinical intervention research. The Core has three components: the Mouse Behavioral Phenotyping Laboratory, the Confocal and Multiphoton Imaging Facility, and the Brain Imaging Analysis Service (for processing data from magnetic resonance (MRI) and diffusion tensor (DTI) imaging). By spanning multiple aspects of mouse model evaluation and use, these components provide a basis for integrative, translational neuroscience within the UNC IDDRC. The Core proposes four objectives to support high-caliber mouse model research: A.I. Provide innovative and translational behavioral phenotyping for genetic and environmental mouse models of neurodevelopmental disorders. The Mouse Behavioral Phenotyping Laboratory offers researchers a multifaceted test regimen, including assays for sensory, motor, social, emotional, and cognitive function, and approaches for neonatal behavior and preclinical drug screens. The PC also provides expertise, training, and access to a range of automated measurement systems for state-of-the-art phenotyping. A.2. Provide consultation, hands-on training, and cutting-edge resources for confocal, multiphoton, and widefield imaging. The Confocal and Multiphoton Imaging Facility offers a state-of-the-art microscopy laboratory, with multiple systems for evaluation of neural tissue in vitro and in living mice. Facility staff provide consultation and hands-on training in molecular and cellular microscopy techniques, including utilization of optogenetic and photosensitive probes, automated time-lapse imaging of neurons and glia, and multiphoton imaging of spatiotemporal dynamics in neuronal migration and connectivity in intact, living embryonic brains. A.3. Develop, utilize, and disseminate advanced methods for analysis of MRI and DTI scans from animal IDD models. The Brain Imaging Analysis Service devises innovative strategies for the processing and interpretation of brain imaging data, and methods to track abnormalities in neural development and function. The Service works to validate and optimize new methods to allow automated volumetric and connectivity analysis in MRIs of the developing rodent brain, and to validate measures applicable to both human and animal scans. Novel processing pipelines for segmentation and atlas-building, developmental brain atlases, and other critical tools for morphometric and functional analyses, are made publicly available. A.4. Facilitate integrative and multidisciplinary IDDRC research. The correlation of complementary mouse phenotypes, such as behavioral responses, dendritic morphology, cortical architecture, and regional brain volume and connectivity, provides a powerful approach to identify the mechanistic basis of abnormalities relevant to neurodevelopmental disorders. By combining behavior, microscopy, and neuroimaging, the PC offers IDDRC investigators the expertise, infrastructure, and collaborative opportunities for multidisciplinary research using mouse models. The PC is also a source of information on services provided by other UNC core facilities, and works to maintain strong connections with the Clinical Translational Core to enhance the relevance of mouse model work to studies in humans.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD079124-02
Application #
8740536
Study Section
Special Emphasis Panel (ZHD1-DSR-H)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$328,420
Indirect Cost
$112,354
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Lyu, Ilwoo; Kim, Sun Hyung; Girault, Jessica B et al. (2018) A cortical shape-adaptive approach to local gyrification index. Med Image Anal 48:244-258
Song, Liujiang; Llanga, Telmo; Conatser, Laura M et al. (2018) Serotype survey of AAV gene delivery via subconjunctival injection in mice. Gene Ther 25:402-414
Giles, Jareca M; Whitaker, Julia W; Moy, Sheryl S et al. (2018) Effect of Environmental Enrichment on Aggression in BALB/cJ and BALB/cByJ Mice Monitored by Using an Automated System. J Am Assoc Lab Anim Sci :
Sidorov, Michael S; Judson, Matthew C; Kim, Hyojin et al. (2018) Enhanced Operant Extinction and Prefrontal Excitability in a Mouse Model of Angelman Syndrome. J Neurosci 38:2671-2682
Mostapha, Mahmoud; Kim, SunHyung; Wu, Guorong et al. (2018) NON-EUCLIDEAN, CONVOLUTIONAL LEARNING ON CORTICAL BRAIN SURFACES. Proc IEEE Int Symp Biomed Imaging 2018:527-530
de Dumast, Priscille; Mirabel, Clement; Paniagua, Beatriz et al. (2018) SVA: Shape variation analyzer. Proc SPIE Int Soc Opt Eng 10578:
Fish, E W; Wieczorek, L A; Rumple, A et al. (2018) The enduring impact of neurulation stage alcohol exposure: A combined behavioral and structural neuroimaging study in adult male and female C57BL/6J mice. Behav Brain Res 338:173-184
Bailey, Rachel M; Armao, Diane; Nagabhushan Kalburgi, Sahana et al. (2018) Development of Intrathecal AAV9 Gene Therapy for Giant Axonal Neuropathy. Mol Ther Methods Clin Dev 9:160-171
Tu, Liyun; Styner, Martin; Vicory, Jared et al. (2018) Skeletal Shape Correspondence Through Entropy. IEEE Trans Med Imaging 37:1-11
Lyu, Ilwoo; Perdomo, Jonathan; Yapuncich, Gabriel S et al. (2018) Group-wise Shape Correspondence of Variable and Complex Objects. Proc SPIE Int Soc Opt Eng 10574:

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