The UC Irvine Center for Neural Circuit Mapping has been awarded a five-year, $1.4 million National Institutes of Health T32 grant to establish a training program for Alzheimer’s disease research. The funds will support projects that hold significant promise for clinical translation to the condition, which remains one of our most pressing medical challenges. An interdisciplinary team of 29 faculty members will mentor and support pre- and postdoctoral fellows, employing state-of-the-art approaches to expand the mechanistic understanding of brain disorders through neural circuit mapping. This emerging field is anticipated to drive new therapeutic strategies in the coming decades. “The program will emphasize the development of novel tools and methodologies for early detection, diagnosis and treatment of Alzheimer’s disease and other dementias,” said principal investigator Xiangmin Xu, UCI Chancellor’s Professor of anatomy & neurobiology and director of the CNCM. “Age-related cognitive impairments represent both a major health and socioeconomic concern in the U.S. and globally. The next generation of scientists in this program will lead the charge in understanding and ultimately curing these complex neurological conditions.” Todd Holmes, professor of physiology & biophysics, is co-principal investigator.

Visit the UCI Newsroom Article for more information.

Research on the degu (Octodon degus) by members of the CNCM and Xu lab was recently featured in The Transmitter, a neuroscience-focused online publication. Calli McMurray’s piece recounts the history of degus in the study of Alzheimer’s disease, showcases our publication on degu neurodegenerative features, and comments on future directions for the model.

Read the full story here.

A new study published in The Journal of Neuroscience by UCI School of Medicine researchers explores how AD affects the brain’s wiring, concentrating on a specific brain area called the subiculum, one of the first brain areas impacted by AD. This opens the door to exciting, innovative treatments for AD that focus on the possibility of repairing impaired brain circuitry rather than changing brain chemistry.

Led by Xiangmin Xu, PhD, a UCI Chancellor’s Professor of anatomy and neurobiology and director of the Center for Neural Circuit Mapping (CNCM), the research team utilized an advanced technique known as monosynaptic rabies viral tracing in a mouse model of AD and normal mice to track how brain connections to the subiculum change with age, as well as between males and females. The study revealed that these connections, particularly those from areas involved in learning and memory, changed differently for males and females and with age, suggesting that AD may disrupt the brain’s networks in complex ways that contribute to memory and learning problems. These findings are in general agreement with the understudied observation that AD impacts male and female AD patients differently.

“Our study is the first to use a novel viral genetic tool to map neuronal circuit changes of the subiculum in AD,” said Xu. “Because circuit defects in AD occur long before symptoms, AD treatments may be more effective by addressing the disease earlier.”

Visit the UCI Newsroom Article for more information.

A research team co-led by the University of California, Irvine, Stanford University and the University of California, San Diego has discovered that there are special neurons dedicated to representing the convex and concave features of environments (commonly referred to as “corners”) in their study of the brain’s spatial mapping system. 

The study titled “Subicular neurons encode concave and convex geometries” is published today online in the journal Nature. The discovery was made possible by extensive and close collaboration among Drs. Yanjun Sun (Stanford), Douglas A. Nitz (UCSD), Xu Xiangmin (UCI) and Lisa Giocomo (Stanford). Their findings have implications in understanding how our abilities of spatial navigation and environmental explorations are affected in aging and Alzheimer’s disease.

Read more here: UCI School of Medicine News

“A research team led by the University of California, Irvine has created 20 new recombinant rabies viral vectors for neural circuit mapping that offer a range of significant advantages over existing tools, including the ability to detect microstructural changes in models of aging and Alzheimer’s disease brain neurons.

The study published today online in the journal Molecular Psychiatry, introduced proof-of-concept data demonstrating the power of these new vectors, which express a range of improved fluorescent proteins to provide expanded multi-scale multi-modal capabilities. Naturally occurring rabies infections target the nervous system.  Scientists harnessed this tendency to create engineered forms of the rabies virus that are coupled to sensors and other payloads – for example, some respond to light by turning bright green and act as tracers that map brain circuits.

‘Viral genetic tools are critical for improving anatomical mapping and functional studies of cell-type-specific and circuit-specific neural networks,’ said Xiangmin Xu, co-corresponding author and UCI Chancellor’s Professor of anatomy & neurobiology and director of the Center for Neural Circuit Mapping. ‘These new variants significantly enhance the capability and reach of neural labeling and circuit mapping across microscopic and macroscopic imaging scales and modalities, including 3D light and X-ray microscopy. We will make these new tools readily available to the neuroscience community through our established service platform at the CNCM.'”

Read more here: UCI News

CNCM has released it’s first annual newsletter! This newsletter covers what we did last year as a center and showcases what there is to look forward to this year and beyond. There is also updates from our Viral Core, Conference Announcements, and Job Listings.

The full newsletter can be read here.

As announced by Vice Chancellor, Steve Goldstein, MD, PhD, FAAP on January 18, 2024, the Center for Neural Circuit Mapping Translational Neuroscience Program has been named one of the 12 high-impact, interdisciplinary research programs that has been selected for the new building and adjacent space.

“At 215,000 square feet, the building is slated to be the largest interdisciplinary discovery and translational research hub on the West Coast. Scheduled to open in 2025, it is made possible by the extraordinary generosity of Adeline Mah, MD, and Robert Mah, PhD, through their Falling Leaves Foundation.

The Falling Leaves Foundation Medical Innovation Building is an embodiment of our collaborative One Health alliance, bringing together talent from across Health Affairs and attracting new recruits from around the globe. It will empower our clinicians and scientists to cure blindness, unlock breakthrough cancer treatments, revolutionize the treatment of neurological disorders, and harness genetics, proteomics and cutting-edge technologies to treat rare diseases and prevent common illnesses.”

For more information regarding the new project see here.

“A first-of-its-kind study led by the University of California, Irvine has revealed a new culprit in the formation of brain hemorrhages that does not involve injury to the blood vessels, as previously believed. Researchers discovered that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds, offering deeper insights into how they occur and identifying potential new therapeutic targets for treatment and prevention.”

Read more here: https://news.uci.edu/2023/11/20/uc-irvine-led-study-is-first-to-find-brain-hemorrhage-cause-other-than-injured-blood-vessels/

“In this webinar, produced with support from Vizgen, Xiangmin Xu, PhD, will introduce several single-cell and spatial multi-omics technologies and describe how they can be used to improve our mechanistic understandings of brain circuit plasticity and neurodegenerative diseases. You will also learn about the University of California Irvine (UCI) Center for Neural Circuit Mapping (CNCM), which has emerged as a hub for new technology and resource development in the field of neuroscience, and their efforts to develop single-cell spatial multi-omics tools.”

This webinar originally aired on September 7th, 2023. For more information and to watch the webinar recording, please see the genengnews website article here: https://www.genengnews.com/topics/omics/rewiring-the-brain-applying-spatial-omics-to-neural-plasticity-and-neurodegenerative-diseases/

“The third annual conference hosted by the UC Irvine Center for Neural Circuit Mapping (CNCM) was held on August 21–23, 2023, at the Beckman Center of the National Academies of Science and Engineering in Irvine, California. Additional events also took place on August 24 on the UC Irvine campus. Hurricane Hillary generated additional anticipation ahead of the conference as she was forecasted to hit Irvine the night before the meeting, and to be the biggest storm in Irvine in ~100 years! To everyone’s relief, Hillary mostly petered out and was downgraded to a tropical storm by Saturday night. Thus, despite the “virtual option” we made available, nearly everyone attended the conference in person.”

Read the full meeting report on Nature.com here: https://www.nature.com/articles/s41380-023-02308-4