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Experiencing a loss of spatial awareness is one of the initial and most unsettling symptoms of progressed Alzheimer’s disease. Now, a fresh investigation from the University of Michigan reveals insights into a distinctive neuron that may be pivotal in comprehending this phenomenon.

The retrosplenial cortex is a cerebral area that has historically been associated with spatial navigation and is recognized to be compromised early in individuals diagnosed with Alzheimer’s disease. Researchers have recently pinpointed a singular neuron with an exceptional function in the retrosplenial cortex. They discovered that specialized neurons can encode a person’s sense of direction at all moments, irrespective of whether the individual is stationary or in motion.

“This type of cell seems uniquely adapted to address a fundamental survival challenge: identifying your location and orientation consistently—whether you’re at your desk or jogging in the park,” remarked Omar Ahmed, associate professor of psychology and the lead author of the research, which is featured in the journal Progress in Neurobiology.

The findings, as noted by Ahmed, offer a mechanistic clarification for why animals can unconsciously assess and recall their position in their surroundings. This ability is crucial for survival: it enables creatures to navigate their location, identify potential escape routes (especially when predators are nearby or in emergency situations), and swiftly orient themselves to the nearest exit, taking the most efficient escape path.

“These neurons exhibit distinct characteristics, express diverse genes, and process data differently from all adjacent neurons. A significant distinction relates to a brain metabolite known as acetylcholine that increases during attention or physical activity,” he stated.

Acetylcholine strongly stimulates various neuron types and alters their method of information encoding. However, the particular retrosplenial neurons do not react to acetylcholine in this manner. Instead, they can reliably monitor head movement, assisting in maintaining orientation continuously, regardless of the person’s activities or focus level, Ahmed explained.

This revelation may elucidate why individuals with Alzheimer’s frequently become lost in familiar environments. Ahmed’s research team is examining how these neurons operate in mouse models of Alzheimer’s in the laboratory while exploring alterations in human brains impacted by the condition.

“Individuals facing neurodegenerative disorders such as Alzheimer’s disease or Parkinson’s disease can find it challenging to navigate home, even in well-known areas,” he noted. “By deciphering the role of these unique neurons in the retrosplenial cortex, we aim to eventually restore or maintain this vital function.”

The study’s co-authors include Izabela Jedrasiak-Cape, Chloe Rybicki-Kler, Isla Brooks, Megha Ghosh, Ellen Brennan, Sameer Kailasa, Tyler Ekins, and Alan Rupp.

The investigation received support from the National Institutes of Health R34NS127101 (Ahmed); NIH R01MH129282 (Ahmed); NIH P50NS123067 (Ahmed); Alzheimer’s Association Grant AARG-NTF-21–846572 (Ahmed); NIH T32-DC000011 (Rybicki-Kler, Ekins); NIH T32- DA007268 (Ekins); NIH T32-NS076401 (Brennan, Rybicki-Kler); and National Science Foundation graduate fellowship (Brennan).

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