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UCI study reveals critical role of new brain circuits in improving learning and memory for Alzheimer’s disease treatment

Xiangmin Xu, PhD
UCI School of Medicine
Xiangmin Xu, PhD, an anatomy and neurobiology professor in the UCI School of Medicine led a team of scientists to discover how newly identified neural circuits in the brain’s hippocampal formation play a critical role in object-location learning and memory.

Irvine, Calif. – September 23, 2019 - A University of California, Irvine-led team of scientists has discovered how newly identified neural circuits in the brain’s hippocampal formation play a critical role in object-location learning and memory.

The study, published today in Nature Neuroscience, was led by Xiangmin Xu, PhD, an anatomy and neurobiology professor in the UCI School of Medicine, and conducted in collaboration with Douglas A. Nitz, PhD, professor and chair of the Department of Cognitive Science at the University of California, San Diego; Qing Nie, PhD, Chancellor's Professor of mathematics and developmental and cell biology at UCI; and, Todd C. Holmes, professor and vice chair of UCI’s Department of Physiology & Biophysics.  

Loss of object location memory is one of the key impairments in Alzheimer’s disease (AD), the most common form of dementia in the elderly.   These new findings in hippocampal circuit mechanisms provide an intriguing new target to counteract AD-related memory impairments. 

“Our study was made possible by new viral genetic based mapping approaches for examining connectivity between structures.  These new mapping tools enabled us to identify novel circuits within and between the hippocampus and cortex,” said Xu. 

Xu and his colleagues used monosynaptic rabies retrograde tracing and herpes (H129)-based anterograde tracing to establish new cortico-hippocampal circuitry associated with subiculum (SUB) projections to hippocampal CA1. Xu and an international team of investigators was recently awarded an NIH BRAIN Initiative grant to develop new H129 viral tracers as a brain mapping tool for use by the entire neuroscience community.

The team revealed the hippocampal sub-circuit mechanism highly relevant to learning and memory disorders including Alzheimer's disease.  These findings may be used to better treat Alzheimer’s disease and other neurological disorders, delay their onset, and possibly prevent them from developing in the first place.

This study was supported by the National Institutes of Health, including a BRAIN Initiative grant and other grants, the National Science Foundation, and the Simons Foundation.

About the UCI School of Medicine: Each year, the UCI School of Medicine educates more than 400 medical students, as well as 200 doctoral and master’s students. More than 600 residents and fellows are trained at UC Irvine Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and master’s degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/master’s in public health, or an MD/master’s degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (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 som.uci.edu.

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