Functional Visual Core (Core D)

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CORE D: Abstract The foremost objective of the Structural and Functional Visualization Core is to provide state of the art imaging services to the IDDRC community, including both conventional and confocal microscopy, whole animal MRI acquisition and analysis support. To attain this goal, the core has been redesigned to provide comprehensive imaging services for IDDRC researchers working at on any aspect of the genetic and environmentally-induced developmental diseases affecting nervous system development and function. The research ongoing in the IDDRC spans basic scientists using reductionist approaches to elucidate the mechanisms specific to intellectual developmental disabilities (IDDs) to clinicians assessing therapeutic interventions for patients. To accommodate all of their imaging requirements, we are now providing access to three light microscopy cores, including a microscopy suite dedicated to IDDRC researchers, two MRI facilities and the technical support needed to initiate and complete any imaging analysis. Many IDDRC researchers have imaging systems within their own laboratories, however they are often insufficient to meet their demand and are never comprehensive. Being able to access the IDDRC-supported microscopy cores thus both adds capacity and provides technical resources not otherwise available, permitting researchers to refocus their studies in novel and innovative directions. A second key objective of the Structural and Functional Visualization Core is to develop new technologies for visualizing biological samples and in turn provide them to IDDRC researchers. Here, we focus on [1] developing smaller lighter one-photon miniaturized fluorescent microscopes for live imaging neural activity in freely moving animals (1-3) and [2] refining the methods for CLARITY, a protocol that renders tissue transparent (4, 5), thereby permitting unparalleled visual acuity into the complex circuitry of the brain. These techniques offer the promise of a holistic approach to cutting edge imaging, permitting IDDRC researchers to translate mechanism into therapy. For example, researchers investigating a specific intellectual disorder, such as Dup15q syndrome (see model project), will be able perform MRI on patients to identify the affected region of the brain, implant miniaturized microscopes in rodent models to perform in vivo i m a g i n g to examine how the firing patterns of specific populations of neuron are mechanistically altered by the disease, while concomitantly examining putative aberrant circuit formation using light microscopy coupled with CLARITY. Finally, this core also supports the efforts of all the other cores, offering IDDRC researchers the ability to both probe molecular and cellular function at any level from the sub-cellular to living animals and determine the consequence of therapeutic interventions.