CNCM leaders publish new guide for viral tracers in neural circuit mapping

The CNCM executive committee members, Xiangmin Xu, Rozanne Sandri-Goldin, Todd Holmes and Bert Semler (from left to right) are major authors for the Neuron primer article.

Center for Neural Circuit Mapping established to disseminate molecular tools to the worldwide neuroscience community

Irvine, CA – August 4, 2020 – Researchers from the newly-established Center for Neural Circuit Mapping at the University of California, Irvine School of Medicine evaluate the properties of anterograde and retrograde viral tracers, comparing their strengths and limitations for use in neural circuit mapping. Results were published today as a primer in Neuron.

The article provides a comprehensive comparison of anterograde and retrograde viral and non-viral tracers for neural circuit analysis and describe neural circuit tracing history and background.  It also examines the specific viruses used for neuroscience research, and provides essential information to guide other researchers on their choice of viral tracers.

Viral tracers are important tools for neuroanatomical mapping and genetic payload delivery. Genetically modified viruses allow for cell-type specific targeting, and overcome many limitations of non-viral tracers.

“A central goal of modern neuroscience research is to understand the cell-type specific connections between different regions of the brain and the detailed circuit organization within them,” said lead author Xiangmin Xu, PhD, professor of anatomy and neurobiology, and director of the new Center for Neural Circuit Mapping. “Our primer evaluates currently applied anterograde and retrograde viral tracers and provides practical guidance on experimental uses, along with key technical and conceptual considerations for developing new safer and more effective anterograde trans-synaptic viral vectors for neural circuit analysis in multiple species.”

Naturally occurring viruses have been used for neural circuit tracing for decades by exploiting the natural properties of viral propagation and transmission.  Genetic modifications of such viruses have led to many improvements for neuroscience applications.  In addition to anatomical mapping, genetically modified viral tracers have greatly facilitated functional studies of cell-type specific and circuit-specific neural networks in the brain. 

Xu, along with other UCI School of Medicine investigators involved in the primer, including Rozanne Sandri-Goldin, PhD, chancellor’s professor and chair of microbiology and molecular genetics, Todd Holmes, PhD, professor and vice chair of physiology and biophysics, and Bert Semler, PhD, distinguished professor of microbiology and molecular genetics and director for the UCI Center for Virus Research, recently launched the Center for Neural Circuit Mapping (CNCM) at the UCI School of Medicine.  The CNCM focuses on neural circuit studies and new viral-genetic technology development. A critical component of the new center is the creation of a viral production facility to disseminate new molecular tools to the worldwide neuroscience community. 

“Using new genetic-viral tools, our main goal with the CNCM is to advance the study of neural circuits using animal models to define mechanisms and pathways that underlie neurodevelopmental, neuropsychiatric and neurodegenerative disorders,” said Xu. “Understanding the brain’s neural circuitry is critical for successful translational progress in better treating these diseases.”

The primer article and the new Center for Neural Circuit Mapping are supported in part by the National Institutes of Health’s BRAIN Initiative, the Brain & Behavior Research Foundation and the UCI School of Medicine.

URL: https://som.uci.edu/news_releases/New-guide-for-viral-tracers-neural-circuit-mapping.asp

New discovery reveals brain network mechanism that causes spatial memory impairment in Alzheimer’s disease

Irvine, CA – July 21, 2020 – Patients with Alzheimer’s disease frequently suffer from spatial memory loss, such as no recognition of where they are and forgetting where they put their belongings. They often show a wandering symptom, which is also a feature of spatial memory impairment. Until now, the brain network mechanism that causes spatial memory impairment had been unclear.

Published today in Neuron, the study titled “Disrupted place cell remapping and impaired grid cells in a knockin model of Alzheimer’s disease” reveals how the normal brain network function of hippocampus cells, which work to discriminate distinct spatial environments in a process called “remapping,” was disrupted in Alzheimer’s disease.  The study, done on Alzheimer’s disease model mice, found that this disruption of hippocampus is most likely caused by activity impairment of the entorhinal cortex, a brain region that supplies information to the hippocampus.

“We recorded the brain cell activity in the hippocampus, which is the memory center of the brain, responsible for spatial memory, among other things,” said Kei Igarashi, PhD, assistant professor in the Department of Anatomy & Neurobiology at the University of California, Irvine School of Medicine and CNCM member.  “Our findings could lead to the development of a method to reactivate brain activity of the entorhinal cortex, which may help establish new treatments for preventing the progression of spatial memory impairment in Alzheimer’s disease patients.” 

Igarashi has been studying brain network mechanisms for Alzheimer’s disease since he started his lab in 2016. “Our memory comes from activities of the brain network. To find out the cure for memory impairment in Alzheimer’s disease, we need to understand how the network function is impaired,” he said.

Original URL: https://www.som.uci.edu/news_releases/brain-network-mechanism-Alzheimers.asp