Ann Arbor Times

Researchers at the University of Michigan have identified a unique type of neuron in the retrosplenial cortex that may help explain why people with Alzheimer’s disease often lose their sense of direction. The findings were published in the journal Progress in Neurobiology.

The retrosplenial cortex is known to play a role in spatial orientation and is affected early in Alzheimer’s disease. The study describes how specialized neurons in this brain region are able to encode an individual’s sense of direction continuously, regardless of whether they are stationary or moving.

“This cell type appears uniquely evolved to solve a basic survival problem: knowing where you are and which way you’re facing at all times—whether you’re sitting in your office or out for a run,” said Omar Ahmed, associate professor of psychology and senior author of the study.

Ahmed explained that these neurons differ from others nearby because they look different, express different genes, and process information differently. A key distinction involves acetylcholine, a brain chemical that increases during periods of attention or movement. While acetylcholine strongly activates most other neurons and alters how they encode information, these unique retrosplenial neurons do not respond to it in the same way. Instead, they consistently track head rotation and help maintain orientation regardless of activity level or attention.

“These neurons look different, express different genes and process information in different ways compared to all their neighboring neurons. One of these key differences relates to a brain chemical called acetylcholine that increases when we are paying attention or running,” he said.

Acetylcholine strongly activates other types of neurons and changes the way they encode information. However, the unique retrosplenial neurons do not respond to acetylcholine in this way. Instead, they can consistently track head rotation, helping to keep track of orientation at all times, regardless of what you are doing or how much attention you are paying, Ahmed said.

This research may clarify why disorientation occurs early for those with Alzheimer’s disease. Ahmed’s team is currently studying how these neurons function using mouse models as well as examining human brains affected by the disorder.

“People living with neurodegenerative conditions such as Alzheimer’s disease or Parkinson’s disease can struggle to find their way home, even in familiar surroundings,” he said. “By understanding these unique neurons in the retrosplenial cortex, we are working towards the goal of one day restoring or preserving this critical function.”

The study was conducted by Izabela Jedrasiak-Cape, Chloe Rybicki-Kler, Isla Brooks, Megha Ghosh, Ellen Brennan, Sameer Kailasa, Tyler Ekins and Alan Rupp alongside Ahmed. Funding for the research came from several National Institutes of Health grants as well as support from the Alzheimer’s Association and National Science Foundation graduate fellowships.