As the brain ages, cognitive functions decline, with working memory – a form of short-term memory necessary for reasoning, decision-making, and behavior – among the earliest affected. The brain’s prefrontal cortex is crucial in working memory, showing sustained activity during memory-guided behavior. A recent study in mice found that aging reduces the prefrontal cortex’s ability to maintain working memory, with older mice showing less effective communication between memory-coding neurons.

Using imaging techniques to see how neurons behave during memory tasks involving touch and sound, researchers tracked brain activity in mice of varying ages. They also used light-based interventions to temporarily disrupt brain activity, observing how this affected the animals' ability to perform the tasks.

They discovered that with aging, the prefrontal cortex had fewer neurons responsible for managing actions, and the signals from these neurons weakened. Furthermore, whereas young mice used both broad and specific memory strategies, older mice mainly relied on specific strategies, indicating a subtle decline in the brain’s memory circuits over time.

The researchers also observed a drop in the resting brain connections among neurons managing actions, beginning around middle age. This drop in connections became even more pronounced when the mice were doing tasks, suggesting that the brain’s ability to retain thoughts might weaken with age. Additionally, the brains of middle-aged mice were more easily disrupted by light-based interventions, hinting at a greater risk to their thought-retention processes as they age.

The findings in this mouse study suggest that aging leads to a marked decrease in brain connectivity and neuron activity in the prefrontal cortex, affecting memory retention and making it more susceptible to disruptions. The blood-brain barrier is a critical player in brain connectivity, and its impairment during aging contributes to cognitive dysfunction. Learn more in this episode featuring Dr. Axel Montagne.