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Cartographers of the brain

Contributed by UCI News:

UCI’s Center for Neural Circuit Mapping is redrawing our understanding of mechanisms underlying several common disorders

by Ian Anzlowar, UCI | November 18, 2020
Cartographers of the brain

“Our goal is to reveal the molecular changes that occur during the course of Alzheimer’s, impacting learning and memory, and identify a route toward early detection and new drug therapies for the disease,” says Xiangmin Xu, director of UCI’s Center for Neural Circuit Mapping. Steve Zylius / UCI

Thanks to Xiangmin Xu and his team at the UCI School of Medicine’s Center for Neural Circuit Mapping, lazy eye, Alzheimer’s and other neurological diseases could become a thing of the past.

Opened earlier this year, the unit focuses on basic neuroscience research, advancing knowledge of the brain by defining mechanisms and pathways that underlie neurodevelopmental, neuropsychiatric and neurodegenerative disorders.

“Our 30 to 40 investigators can join forces to tackle large-scale research projects with potentially far-reaching impact, including mechanistic studies of Alzheimer’s disease,” says director Xu, professor of anatomy & neurobiology.

The facility’s first project – supported in part by the National Institutes of Health – was on amblyopia, more commonly known as lazy eye. Stemming from unequal visual development early in life, it causes the brain to ignore signals from the weaker eye, resulting in a loss of neural connectivity and further impairing sight in that eye.

By subcutaneously administering subanesthetic ketamine, an antidepressant traditionally used for pain management, Xu and his researchers were able to reverse the effects of amblyopia and reactivate adult neural connectivity. In August, their findings were published in Current Biology, and while further testing is required to determine the full implications of this discovery, it could have a significant impact on the treatment of this disorder.

Additionally, with a $3.8 million award from the National Institute on Aging, center members are studying molecular changes in the brain caused by Alzheimer’s. Using mouse models that mimic the neurodegenerative disease, they’re exploring how the epigenome of major cell types, including neurons and non-neuronal cells such as astrocytes and microglia, shapes hippocampal circuit activity and behaviors during Alzheimer’s pathogenesis.

The research involves viral tracing, a method of implanting a harmless virus into a specific neuron in the brain and tracking its movement along neural pathways to determine cellular connectivity. Tracers travel along the interconnected pathways and, as these connections become increasingly damaged, plot the disease’s progression and its effect on memory loss. Viral tracers are important tools for neuroanatomical mapping and will allow researchers to specifically target affected neurons with possible gene-editing or -repairing treatments in the future.

“Our goal is to reveal the molecular changes that occur during the course of Alzheimer’s, impacting learning and memory, and identify a route toward early detection and new drug therapies for the disease,” Xu says.

A critical component of the Center for Neural Circuit Mapping is the creation of a viral production facility to disseminate these novel molecular tools for amblyopia, Alzheimer’s and other potential diseases to the global neuroscience community.

“Currently, there is no cure for Alzheimer’s disease,” Xu says. “And with millions of people, including 5.5 million Americans, affected by this debilitating condition, it’s increasingly critical that we develop superior early diagnostic techniques and new treatment strategies to care for them.”

While the center is focused on cutting-edge breakthroughs in neuroscience, its staff is not limited to professors and postdoctoral students. The unit is active in UCI’s Undergraduate Research Opportunities Program, and before the coronavirus outbreak, more than 20 undergrads worked there. They’re trained by postdocs to better prepare them for careers in biomedical research. They also employ methods common in computer science and engineering, gaining wide-ranging experience in real-world situations.

“The Center for Neural Circuit Mapping provides a strong infrastructure and many resources for investigators to develop new tools to further studies,” Xu says, “and it will help UCI researchers obtain federal funding for our critical work.”