George Vidal, Ph.D. - US grants

DESCRIPTION (provided by applicant): When the brain is developing, it uses specific rules to determine if two neurons should form a synapse between them or not. For example, neurons that fire together will often wire together, and those that are out of synch, lose their link These synaptic plasticity rules are very important in determining what portion of the cortex and which cells will be devoted to certain processes, such as binocular vision. The Shatz laboratory has found that PirB (paired immunoglobulin-like receptor B), an immune receptor found normally in neurons and having a human ortholog, acts as a brake on plasticity in the mouse visual cortex. Removing PirB genetically in the mouse (i.e. removing the brake) enhances plasticity in visual cortex. Removing the brake on cortical plasticity in the adult could be important in recovering from injury (e.g. stroke), neurodegenerative disease (e.g. Alzheimer's), or developmental disorders (e.g. autism or amblyopia). Therefore, one of the greatest priorities of the lab is to understand the cellular and molecular mechanisms that underlie the enhanced plasticity that comes from removing PirB genetically from the mouse, or when PirB is directly blocked. The first goal of this project is to understand if PirB has an effect on synaptic plasticiy rules (such as the rule fire together, wire together) that cause plasticity to decrease in adulthood. This will be done by comparing normal brains and brains lacking PirB using cortical slice electrophysiology. The second goal of this project is to directly block the function of PirB and see if these and other plasticity rules can be changed immediately. This will be observed using cortical slice electrophysiology and live two-photon excitation microscopy. If cells do modify their structure and synaptic plasticity rules, then acutely removing the brake by blocking PirB could provide new ways to overcome injury, disease, or developmental disorders of the brain.

An award is made to James Madison University (JMU) to fund the acquisition of an advanced light microscope system with enhanced resolution, sensitivity, and speed to serve as a regional resource for research and education. The instrumentation will expand the scope of research and education in multiple departments at JMU, in neighboring institutions, and in the surrounding community by enabling faculty and students to study microscopic biological and physical processes at spatiotemporal resolutions exceeding those offered by conventional light microscopes. JMU and its neighboring colleges are primarily undergraduate institutions and are committed to engaging students in learning through faculty-mentored research. Indeed, students are responsible for approximately 90% of the total research use of the core microscopy facility. In doing so, they not only conduct original research, but also become competent microscopists. The funded microscope system will become a key component of the core facility and will enhance student research training by exposing them to advanced imaging technologies. This instrumentation will also benefit formal upper-division courses at JMU such as Developmental Neurobiology and Biophysical Chemistry by providing students with practical and theoretical education in cutting-edge light microscopy techniques. Moreover, in an effort to expand the impact on undergraduate research training, the investigators will develop a scientific image data management training module, focusing on best-practices that promote rigor and reproducibility in scientific research. The module materials and outcomes will be disseminated to inform scientific data management training in other sub-disciplines of science and at other institutions. Finally, the microscope system will support general science, technology, engineering, and math (STEM) education in the surrounding northern Shenandoah Valley region through outreach to neighboring high schools and colleges. A new outreach module incorporating hands-on classroom activities and a remote demonstration of the new microscope will be developed to teach students the concept of size at the micro-scale and will be offered through JMU’s STEM outreach center.<br/><br/>The funded microscope system will open new investigative avenues for researchers at JMU and in the region by enabling the study of biological and physical processes across broad spatiotemporal scales. While it is useful to study processes within one size regime, it is also essential to study how phenomena are integrated across spatiotemporal scales, e.g., from cells to tissues, molecules to sub-cellular organization, rapid/brief events to slow/long-lived behaviors. The funded microscope will enable the study of how small-scale events and patterns combine to determine larger-scale properties and will, in particular, enable the visualization of very small features and fast processes that are beyond the sensitivity of conventional light microscopes. It will advance the research programs of at least 16 faculty across multiple STEM fields including biology, physics, biochemistry, and science education. Projects that will be particularly impacted include studies of: formation and refining of neuronal connections during development; cell migration; materials that convert between liquid and solid phases depending on physical confinement during flow; how neurons in the eye regulate non-image-forming behaviors; bacterial biofilm structure and development; and cartilage tissue patterning during development.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.