UAMA&A will be taking place on December 13-16, 2023, in Santiago, Chile. This event is organized and cosponsored by IEB (Institute of Ecology and Biodiversity), and the University of California Irvine Center for Neural Circuit Mapping (CNCM).
Registration is open until November 10th but there is early bird discount pricing until October 15th. Please visit https://uamaa23.net/ for more information on the conference.
Irvine, CA – July 25, 2023 – A University of California, Irvine-led team of researchers working at the Center for Neural Circuit Mapping (CNCM) find links between brain disorders and dysfunction of newly identified inhibitory brain cell types.
Different types of brain inhibitory neurons were identified first over 100 years ago by differences in their shape and form, but their functions are still being uncovered.
The gene expression profile of the newly discovered class of inhibitory neurons indicates strong associations with neurological and neuropsychiatric diseases and high energy use.
A team of UCI scientists led by Xiangmin Xu, PhD, professor of anatomy and neurobiology and director for the Center for Neural Circuit Mapping at the UCI School of Medicine, found that a distinct new class of brain inhibitory neurons when functioning abnormally may contribute to neurological and psychiatric conditions, including autism and schizophrenia.
“We’ve discovered a new class of inhibitory neurons in the brain that are implicated in several neuropsychiatric conditions,” said Xu. “These neurons are characterized by their chemical signature of expressing calcium binding protein parvalbumin and the cholecystokinin (CCK) peptide.”
The nervous system uses a balance of excitatory and inhibitory neurons that interact. Without inhibitory neurons, the brain experiences epilepsy and other neurological disorders. The class of neurons that Dr. Xu’s team discovered are very metabolically active and thus require high levels of energy.
“These key inhibitory neurons effectively act as a braking system of the brain to slow down overall activity,” said Xu. “The loss of function of the braking system of the brain leads to abnormal function.”
The team is now studying the very active types of neurons with high energy requirements for potential therapies. They are further examining these neurons to better understand their relationship to neuropsychiatric conditions and their contributions to brain function.
Members of the research team include: Steven F. Grieco, PhD, Kevin G. Johnston, PhD, Pan Gao, B. Maximiliano Garduño,Bryan Tang, Elsie Yi, Yanjun Sun, PhD, Zhaoxia Yu, PhD, Todd C. Holmes, PhD, and Xiangmin Xu, PhD, and their collaborator Gregory Horowitz, PhD, at the University of Washington.
About the UCI School of Medicine
Each year, the UCI School of Medicine educates more than 400 medical students and nearly 150 PhD and MS students. More than 700 residents and fellows are trained at the UCI Medical Center and affiliated institutions. Multiple MD, PhD and MS degrees are offered. Students are encouraged to pursue an expansive range of interests and options. For medical students, there are numerous concurrent dual degree programs, including an MD/MBA, MD/MPH, or an MD/MS degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Program in Medical Education for Leadership Education to Advance Diversity-African, Black and Caribbean (PRIME LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.
Funding will help campus become a national center of neuroscience resources
Xiangmin Xu, Autumn Ivy, Bert Semler, Todd Holmes and Orkide Koyuncu (from left) will expand the production and distribution of cell-type-specific viral targeting reagents. Steve Zylius / UCI
UCI has received a $3.8 million BRAIN Initiative grant from the National Institutes of Health to enhance the production and distribution of cell-type-specific viral targeting reagents that are emerging as critical tools. This funding, leveraging UCI’s designation as a minority-serving institution, will enable the expansion of adeno-associated virus production at the campus’s Center for Neural Circuit Mapping. Xiangmin Xu, UCI professor of anatomy & neurobiology and CNCM director, and Gordon Fishell, professor of neurobiology at Harvard University, are co-principal investigators. “We have a strong neuroscience reagent core facility at UCI and will collaborate closely with Harvard University and the Broad Institute to scale up and optimize production and distribution processes for viruses that they have designed. We are proud that UCI has become a national center of viral resources, which strengthens the U.S. scientific enterprise,” Xu said. Partners also include scientists and trainees from Pomona’s Western University of Health Sciences and Atlanta’s Morehouse School of Medicine, as well as UCI’s Todd Holmes, professor of physiology and biophysics; Bert Semler, Distinguished Professor of microbiology and molecular genetics; Autumn Ivy, assistant professor of pediatrics; and Orkide Koyuncu, assistant professor of microbiology and molecular genetics. This work is supported by NIH award number U24MH13326.
“By shedding light on the intricate molecular changes that occur in Alzheimer’s disease, we anticipate that we will be able to fully characterize the neuronal circuits and disease vulnerability at the cellular level,” says principal investigator Xiangmin Xu, UCI professor and Chancellor’s Fellow of anatomy & neurobiology and director of the campus’s Center for Neural Circuit Mapping.
Irvine, Calif., June 15, 2023 — The University of California, Irvine has received a five-year, $10 million grant from the National Institutes of Health to lead a multi-institutional study of specific brain cell vulnerabilities to abnormal tau protein deposits in regions affected in the early stages of Alzheimer’s disease.
“We’re seeking to gain deeper insights into the intricate cellular and spatial molecular changes behind the loss of cells and connectivity that occurs in this disease,” said principal investigator Xiangmin Xu, UCI professor and Chancellor’s Fellow of anatomy & neurobiology and director of the campus’s Center for Neural Circuit Mapping. “This research has the potential to revolutionize our understanding and may pave the way for the development of targeted therapeutic strategies.”
Current literature offers information about the molecular changes in the brain from a heterogeneous cell population perspective. This project will involve the analysis of single cells and specific brain regions in mouse models to discover the mechanisms by which tau protein deposits influence the occurrence of Alzheimer’s and related dementias.
“We will leverage the team’s strong expertise in single-cell and spatial transcriptomics and epigenomics, which are advanced, state-of-the-art techniques in the study of genes within individual cells and the factors that influence their behavior, to gain new biological insights at an unprecedented cellular and spatial resolution. The strong collaborative infrastructure and resources of the CNCM, supported by the School of Medicine and campus Office of Research, will also be critical to this large-scale, multi-institutional project,” Xu said.
Other UCI team members include Kim Green, professor and vice chair of neurobiology and behavior; Grant MacGregor, professor of developmental and cell biology; and Gopi Meenakshisundaram, professor of computer science. Michael Koob, associate professor of laboratory medicine and pathology, and Timothy Ebner, department head and professor of neuroscience, both from the University of Minnesota, as well as Bing Ren, professor of cellular and molecular medicine at UC San Diego, are the other major investigators on the project.
This work is funded by the NIH’s National Institute on Aging under award number 1R01AG082127.
About UCI’s Brilliant Future campaign: Publicly launched on Oct. 4, 2019, the Brilliant Future campaign aims to raise awareness and support for UCI. By engaging 75,000 alumni and garnering $2 billion in philanthropic investment, UCI seeks to reach new heights of excellence in student success, health and wellness, research and more. The School of Medicine plays a vital role in the success of the campaign. Learn more by visiting https://brilliantfuture.uci.edu/uci-school-of-medicine.
About the University of California, Irvine: Founded in 1965, UCI is a member of the prestigious Association of American Universities and is ranked among the nation’s top 10 public universities by U.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide. For more on UCI, visit www.uci.edu.
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The Center for Neural Circuit Mapping (CNCM), the Center for Hearing Research (CHR), and the Departments of Otolaryngology – Head & Neck Surgery, and Anatomy and Neurobiology cordially invite you to a special lecture by Dr. Fan-Gang Zeng, and a joint reception on May 2 at the Interdisciplinary Science and Engineering Building (ISEB). The events will celebrate Dr. Zeng’s election to the National Academy of Engineering. Our campus and school leaderships will make remarks. Please join us in celebrating the collaborative achievements of the Schools of Medicine, Biological Sciences, Engineering, Information and Computer Science, Social Sciences, Pharmacy, and other academic units.
Organizers: Karina Cramer, Christine Gall, Todd Holmes, Raju Metherate, Virginia Richards, Tjoson Tjoa, and Xiangmin Xu
The main conference will take place at the Beckman Center of the National Academies of Sciences & Engineering near the UCI campus. Additional events will take place on UCI campus. The UCI Center for Neural Circuit Mapping (CNCM) continues to host annual neural circuit conferences, following the success of our in-person 2021 and 2022 conferences. We are looking to host an even more front-of-the-field conference in 2023 with thought leaders in neuroscience who will bring unique perspectives to the theme of integrating the different facets of neural circuits – structure, function, development and disease. Please see our speaker lineup, including Drs. Hongkui Zeng, Silvia Arber, Denis Jabaudon, Alain Chedotal, Tirin Moore, Leah Krubitzer, Guoping Feng, John Rubenstein, Thomas Südhof, Linda Richards and more.
We encourage attendees to submit abstracts, which will be selected for short talks or poster presentations. Abstracts will be included in our conference program book.
Please forward this email to your colleagues and spread the word!
Thanks and best wishes,
Xiangmin Xu, PhD
Director, Center for Neural Circuit Mapping
Professor, Anatomy & Neurobiology
UCI School of Medicine
Chilean degu rodents display behavioral and neuropathological features that resemble human Alzheimer’s Disease
Immunofluorescence confocal microscopy shows that reactive astrocytes (green) surround amyloid plaques (red) in the aged, outbred degu brain.
Irvine, CA – December 19, 2022 – Led by researchers from the University of California at Irvine, a new study reveals that a long-lived Chilean rodent, called Octodon degus (degu), is a useful and practical model of natural sporadic Alzheimer’s Disease. The findings were published today in Acta Neuropathologica Communications.
“We found robust neurodegenerative features in cognitively impaired aged degus, including hippocampal neuronal loss, altered parvalbumin and perineuronal net staining in the cortex, and increased c-Fos neuronal activation in the cortex that is consistent with the neural circuit hyperactivity that are commonly reported in human Alzheimer’s Disease patients,” explained corresponding author Xiangmin Xu, PhD, professor and Chancellor’s Fellow of anatomy and neurobiology in the UCI School of Medicine, and director of the Center for Neural Circuit Mapping. “By focusing on a subset of aged degus that show AD-like behavioral deficits and correlative neuropathology, we establish outbred degus as a natural model of sporadic AD and demonstrate the potential importance of wild-type outbred genetic backgrounds for AD pathogenesis.”
This study was motivated by the need to settle earlier debates of whether degus can be a useful natural model of AD. There is a critical need for non-murine, natural animal models for Alzheimer’s research as particularly highlighted by the NIH RFA “New/Unconventional Animal Models of Alzheimer’s Disease.” The handful of published papers on degus of differing genetic backgrounds yield inconsistent findings about sporadic AD-like pathological features, with notably differing results between lab in-bred degus versus outbred degus.
“We suspect that inconsistent findings between different studies may have been due to comparing neuropathology results from laboratory in-bred colonies versus more genetically diverse outbred degus, relatively low statistical power for sample size, and the absence of behavioral screening,” said Xu.
This study revealed that outbred, aged degus possessing both behavioral and neuropathological characteristics that resemble human AD pathologies, have clear advantages over common rodent models (mice and rats) for studying AD. Further, a portion of the outbred degu population naturally develops additional conditions similar to type-2 diabetes, macular degeneration, and atherosclerosis with age, which provides an avenue to investigate AD comorbidities in the degu.
“Our findings, taken together, show spontaneous AD-like correlative phenotypes in cognitive performance and neuropathology in aged, outbred degus. This supports that aged degus are a useful and practical model of natural sporadic AD,” said Xu.
Zhiqun Tan, PhD, an associate researcher with UCI’s CNCM and UCIMIND, and B. Maximiliano Garduño, a graduate student in the UCI Department of Anatomy & Neurobiology, are co-first authors of the paper. Other members of the research team include Todd Holmes, PhD, from the UCI School of Medicine Department of Physiology & Biophysics; Lujia Chen, a graduate student in biomedical engineering at UCI; and their international collaborators Patricia Cogram, PhD, associate professor, and Pedro Fernández Aburto, PhD, from the Institute of Ecology and Biodiversity at the University of Chile. This study was supported by the National Institutes of Health.
Alzheimer disease (AD) is an age-related progressive neurodegenerative disorder characterized by irreversible cognitive decline and specific pathologic lesions in the brain that greatly impair the lives of individuals suffering from the condition. There are approximately 44 million people suffering from AD worldwide, of which over 90 percent of those cases are late-onset and occur sporadically.
Xiangmin Xu leads a UCI interdisciplinary team – including neuroscientists, engineers, virologists, computer scientists and mathematicians – that is raising new hope for early treatments of crippling brain disorders such as Alzheimer’s, depression and epilepsy. In September, Xu’s Center for Neural Circuit Mapping began collaborating with two other institutions on a five-year project, backed by $126 million in federal funds, to map the human brain in unprecedented molecular detail.
“What is most exciting about our work is that we have the potential to identify early warning signs of disorders such as Alzheimer’s disease when they are still treatable,” he says.
In a key breakthrough, Xu, a professor in the Department of Anatomy and Neurobiology, says he and his collaborators have already discovered ways to reopen windows of neural development in adults, paving the way for previously unthinkable remedies.
LAYING THE GROUNDWORK FOR RNA VACCINES
With life approaching a pre-pandemic norm, Philip Felgner is feeling justifiably proud.
Felgner, 72, UCI’s director of Vaccine Research and Development Center, has spent more than half of his lifetime helping to lay the groundwork for the cutting-edge messenger RNA vaccines that have saved countless lives.
Older vaccines stimulated the body’s immune system with weak or inactive viruses or bacteria. The game-changing new vaccines deployed in the pandemic instead use genetically engineered mRNA to teach cells to make a protein that triggers an immune response.
Felgner’s contributions date to his 1984 discovery of lipofection technology, in which scientists insert genetic material into a liposome – an artificial nanoparticle – to deliver it to cells. Since then, hundreds of other researchers have helped develop the field.
Last year, Felgner was one of seven scientists to win Spain’s prestigious Princess of Asturias Award, but he isn’t resting on his laurels. At the start of the pandemic, in February 2020, his lab began monitoring local virus exposure and later measured the stunning efficacy of the mRNA vaccines.
“My proudest moment is now,” he says, “to see the results of my contribution and those of hundreds of other scientists come to fruition in such a dramatic way.”
Irvine, Calif., Sept. 22, 2022 – The University of California, Irvine will participate in a five-year, multi-institutional, $126 million grant from the National Institutes of Health supporting the BRAIN Initiative Cell Atlas Network. The project aims to describe the cells that make up the human brain in unprecedented molecular detail, classifying them into more precise subtypes and pinpointing their location.
As a full member of BICAN, UCI will receive $10 million to collect, process and characterize a broad range of adult brain specimens. An interdisciplinary UCI team, led by Xiangmin Xu, Ph.D., Chancellor’s Fellow of anatomy & neurobiology and director of the Center for Neural Circuit Mapping, will collaborate with scientists from the Salk Institute for Biological Studies, UC San Diego and Washington University in St. Louis.
Irvine, Calif., June 7, 2022 — The University of California, Irvine has been awarded a five-year, $14 million grant from the National Institutes of Health to study brain circuits that are susceptible to aging and Alzheimer’s disease. The research findings will advance the development of early diagnostic tools and the discovery of new treatment strategies.
Xiangmin Xu, Ph.D., UCI Chancellor’s Fellow of anatomy and neurobiology and principal investigator, will lead an interdisciplinary, multi-institutional team whose goal is to construct comprehensive, high-resolution maps of specific neuron types and their connections in critical brain circuits whose defects correspond with behavioral deficits associated with aging and Alzheimer’s disease.
