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Researchers at the University of California, Irvine have made a groundbreaking discovery by establishing the first direct connection between two neural circuits in the brain’s retrosplenial cortex and their roles in spatial navigation and memory formation. This important finding holds promise for advancing targeted medical interventions for Alzheimer’s disease and other cognitive impairments by pinpointing specific neural pathways for treatment.
The findings were shared in a study published in the journal Molecular Psychiatry, which delineated two distinct types of retrosplenial cortex (RSC) pathways that interact with different brain regions, each demonstrating unique input patterns and functional roles.
Lead author Xiangmin Xu, a distinguished Chancellor’s Professor of anatomy and neurobiology at UC Irvine and the director of the Center for Neural Circuit Mapping, commented on the significance of the research. “Our study reveals how particular circuits within the RSC are integral to various cognitive processes, providing a foundational framework for future investigations and enhancing our understanding of how we learn and retain mental representations of our surroundings,” Xu stated. He emphasized the relevance of this research in understanding the effects of neurodegenerative conditions like Alzheimer’s, which can alter function in specific brain areas, paving the way for innovative treatment strategies.
The retrosplenial cortex is known to connect with several brain regions. The research team concentrated on two principal pathways: the M2-projecting pathway that leads to the secondary motor cortex, and the AD-projecting pathway which connects to the anterior thalamus. Neurons in the M2 pathway play a crucial role in translating spatial thoughts into actions, whereas neurons within the AD pathway are essential for recalling specific locations.
Using cutting-edge viral methodologies, the researchers mapped and individually manipulated these neural connections to observe their functions. The study revealed that disabling M2-projecting neurons impaired the ability to remember object locations and associate actions with particular sites. Conversely, inhibiting AD-projecting neurons led to a diminished capacity for recalling the locations of objects alone.
Xu remarked, “We are building upon these initial findings to study further pathways within the retrosplenial cortex and understand how various types of neurons influence memory and spatial awareness. Our overarching aim is to chart the brain’s ‘GPS system,’ which will enhance our comprehension of navigation and memory formation, as well as help isolate specific neuronal cells and pathways involved in disorders like Alzheimer’s and formulate treatments aimed at those neural circuits.”
The research team included Xiaoxiao Lin, Ali Ghafuri, Xiaojun Chen, and Musab Kazmi, who are or were affiliated with Xu’s lab, along with co-corresponding author Douglas A. Nitz, Chair of cognitive science at UC San Diego.
This significant study received funding from the National Institutes of Health, supported by grants NS078434, MH120020, and U01AG076791.
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