The same brain cells linked to disorientation in Alzheimer’s disease have been preserved—and even slightly increased—across millions of years of evolution.
A new study suggests these neurons are vital to evolutionary survival.
Nature has guarded and amplified them through countless generations, helping mammals instinctively know where they are in their environments.
Charles Darwin first described the remarkable ability of most species to know where they are even without external cues and figure out a direct path to their destination. He called this “dead reckoning.” But this ability to seamlessly navigate between familiar locations is impaired in people who suffer damage to a brain region called the retrosplenial cortex.
“The retrosplenial cortex functions as a subconscious GPS system for our brains. It has specialized neurons that calculate what direction we need to go in to head towards our desired destination,” says Omar Ahmed, University of Michigan associate professor of psychology and senior author of the study.
“The retrosplenial cortex is also activated when we imagine ourselves in a future time or place. So, it’s a remarkable brain region, one that helps us subconsciously understand where we are in our real or imagined world. Unfortunately, the retrosplenial cortex is also one of the first regions to show impairments in Alzheimer’s disease.”
Ahmed’s team had previously discovered a unique type of neuron in the mouse retrosplenial cortex. For this new study, Isla Brooks, a member of Ahmed’s lab and the study’s first author, and Ahmed created advanced AI-based tools to compare the genetic signatures of neurons from the retrosplenial cortex of mice to those from rat retrosplenial cortex. These two species are millions of years apart in the evolutionary tree. Despite this, the unique type of neuron was remarkably well preserved in rats.
The researchers also identified another specialized type of neuron, equally ancient and essential for spatial awareness, and, again, only found in the retrosplenial cortex. This second type of unique neuron was also preserved and slightly amplified across evolution.
“By comparing thousands of genes across thousands of neurons from distinct species, we can ask how specific types of neurons change across evolution,” Ahmed says.
The retrosplenial cortex contains at least two specialized neuron types that are not found anywhere else in the brain.
“It’s easy to imagine why these neurons are of critical importance for the survival of a species and preserved over millions of years of evolution: they help to successfully find one’s way home,” Ahmed says.
Most people living with Alzheimer’s disease suffer from spatial disorientation and cannot find their way home. Ahmed’s lab is now investigating if these unique neurons are also found in the human retrosplenial cortex and what happens to them in Alzheimer’s disease.
“We see neurons in the human brain that physically look like the specialized retrosplenial neurons seen in other species. By understanding how these neurons change in people with Alzheimer’s disease we can work towards targeted therapies to repair the neurons,” Ahmed says.
The research appears in the Journal of Neuroscience.
Support for the work came from the National Institutes of Health and the Alzheimer’s Association.
Source: University of Michigan
