Irvine, Calif., Nov. 14, 2024 — Researchers led by the University of California, Irvine are the first to reveal how two neural circuits located in the brain’s retrosplenial cortex are directly linked to spatial navigation and memory storage. This discovery could lead to more precise medical treatments for Alzheimer’s disease and other cognitive disorders by allowing them to target pathway-specific neural circuits.

The study, recently published online in the journal Molecular Psychiatry, identified two types of RSC pathways, connected to different parts of the brain, each with its own pattern of inputs and functions.

“By demonstrating how specific circuits in the RSC contribute to different aspects of cognition, our findings provide an anatomical foundation for future studies and offer new insights into how we learn and remember the space around us,” said lead and co-corresponding author Xiangmin Xu, UC Irvine Chancellor’s Professor of anatomy and neurobiology and director of the campus’s Center for Neural Circuit Mapping. “This is an important step in understanding how conditions like Alzheimer’s disease and other neurodegenerative disorders affect particular regions of the brain, which will help to inform new approaches and treatments.”

The RSC is linked to multiple regions of the brain. The team focused on two main pathways, the M2-projecting, which is connected to the secondary motor cortex, and the AD-projecting, which is connected to the anterior thalamus. M2 neurons are involved in turning spatial thought into action, while the AD neurons are vital to remembering specific locations.

To observe these circuits in action, researchers used advanced viral tools to map and manipulate the connections separately and evaluate the effects. They found that blocking M2-projecting neurons made it more difficult to remember where objects were located and to associate specific places with actions. Inhibiting AD-projecting neurons only diminished memory of objects’ location.

“We are expanding on these results to explore additional pathways within the RSC, examining how different types of neurons impact memory and spatial orientation,” Xu said. “Our goal is to build a map of the brain’s ‘GPS system.’ This will not only increase our knowledge of how we navigate our world and form memories of it, but also help identify specific brain cells and their pathways contributing to various disorders such as Alzheimer’s disease and develop treatments that target them.”

Other team members were Xiaoxiao Lin, Ali Ghafuri, Xiaojun Chen and Musab Kazmi, all current or former members of Xu’s lab; and co-corresponding author Douglas A. Nitz, professor and chair of cognitive science at UC San Diego.

This work was supported by the National Institutes of Health under grants NS078434, MH120020 and U01AG076791.

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About the University of California, Irvine: Founded in 1965, UC Irvine 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, UC Irvine 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 UC Irvine, visit www.uci.edu.

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