Understanding How Aging Affects Mental Maps and Spatial Memory

The ability to remember the locations of objects, places, and navigational routes—collectively known as spatial memory—is a fundamental aspect of daily life. From recalling where we left our keys to navigating through new environments, spatial memory plays a crucial role. However, it is also one of the earliest cognitive functions to decline with age. This decline can manifest as difficulty in learning new environments or disorientation in unfamiliar places, sometimes serving as an early indicator of dementia.

Recent research conducted by scientists at Stanford Medicine and collaborating institutions has shed light on what occurs in the aging brain during the decline of spatial memory. The study focused on the medial entorhinal cortex, a brain region often compared to the GPS of the brain, responsible for creating mental maps of our environment. The researchers studied mice across three age groups—young, middle-aged, and old—and discovered that activity within this region becomes less stable and less responsive to environmental cues as the mice age. Notably, older mice exhibiting the most impaired activity also showed the greatest difficulty in spatial memory tasks.

Dr. Lisa Giocomo, a neurobiology professor and senior author of the study published in Nature Communications, explained that the medial entorhinal cortex houses grid cells that form a coordinate system for space, akin to longitude and latitude lines on a map. These cells help animals—and humans—navigate by building and updating mental spatial representations. The study involved tracking brain activity in mice as they navigated virtual reality corridors to find hidden rewards. Over repeated trials, all age groups developed specific firing patterns in grid cells that corresponded to learned environments.

However, when tasked with distinguishing and switching between two different spatial tracks that each had unique reward locations, older mice struggled significantly. Their grid cells fired erratically when the environments were alternated, indicating a failure to differentiate between contextual maps. This mirrors human experiences, where older adults often navigate familiar spaces well but find it challenging to learn or adapt to new environments.

Interestingly, some old mice demonstrated exceptional memory capabilities, performing as well as their younger counterparts. These 'super-agers' showed stable grid cell activity and accurate spatial recall. Genetic analysis of these mice revealed differences in gene expression, with 61 genes more active in mice with deteriorated spatial memory. One gene, Haplin4, is associated with supporting neuron stability and may hold potential for future therapeutic strategies.

The findings offer promising insights into the neural mechanisms of spatial memory decline and highlight the variability in aging processes. Understanding why some individuals—and mice—maintain sharper cognitive functions into old age could inform interventions to preserve memory and prevent neurodegenerative diseases.

This research advances our knowledge of the aging brain and opens avenues for developing strategies to maintain spatial orientation and memory throughout aging.