Implicating Striosomes in Age-Related Changes in Decision Making

The brain is very complex, and so the ways in which comparatively simple mechanisms of aging lead to alterations in cognitive function are also very complex. The research here picks up the trail of cause and effect relating to changes in approach-avoidance conflict, a part of decision making, a fair way down the line from first causes, as is the case for much of the work taking place on the aging of the brain. It is nonetheless always interesting to see specific age-related changes in complex traits connected to specific cells and their activity, even when the further connections to underlying mechanisms of aging remain obscure.

The striatum is part of the basal ganglia - a collection of brain centers linked to habit formation, control of voluntary movement, emotion, and addiction. For several decades, researchers have studied clusters of cells called striosomes, which are distributed throughout the striatum. Their function had remained mysterious, in part because they are so small and deep within the brain that it is difficult to image them with functional magnetic resonance imaging.

In recent years, researchers have discovered that striosomes play an important role in a type of decision-making known as approach-avoidance conflict. These decisions involve choosing whether to take the good with the bad - or to avoid both - when given options that have both positive and negative elements. An example of this kind of cost-benefit decision is having to choose whether to take a job that pays more but forces a move away from family and friends. Such decisions often provoke great anxiety.

In a related study, researchers found that striosomes connect to cells of the substantia nigra, one of the brain's major dopamine-producing centers. These studies led the researchers to hypothesize that striosomes may be acting as a gatekeeper that absorbs sensory and emotional information coming from the cortex and integrates it to produce a decision on how to act. These actions can then be invigorated by the dopamine-producing cells.

Researchers found that in older mice (between 13 and 21 months, roughly equivalent to people in their 60s and older), the mice's engagement in learning this type of cost-benefit analysis went down. At the same time, their striosomal activity declined compared to that of younger mice. The researchers found a similar loss of motivation in a mouse model of Huntington's disease, a neurodegenerative disorder that affects the striatum and its striosomes. When the researchers used genetically targeted drugs to boost activity in the striosomes, they found that the mice became more engaged in performance of the task. Conversely, suppressing striosomal activity led to disengagement. The researchers are now working on possible drug treatments that could stimulate this circuit.

Link: https://news.mit.edu/2020/why-learn-motivate-age-decline-1027