The elderly are often unable to adjust to new surroundings. This is partly due to the deterioration of a brain circuit that plays a key role in goal-directed learning, a new study conducted on mice has found.
The results revealed that the faulty activation of this brain circuit mixes both the new and old learning in the elderly mice, thus causing impairment in their ability to select the most appropriate action in response to a changing environment that leads to confusion.
“Flexibility issues in ageing have long been described in other navigation and spatial memory tasks. Here we describe a similar flexibility problem, but applied to goal-directed action, which of course has more detrimental consequences for everyday life and potentially compromises survival,” said J. Bertran-Gonzalez of the University of Queensland in Australia.
This flexibility problem could constitute a first step towards major motivational decline and, in some cases, seed further cognitive conditions and dementia, the researchers noted in the paper published in the journal Neuron.
The team found that the ability to make choices between distinct courses of action depends on a brain region called the striatum, which is located in the forebrain and associated with planning and decision-making. However, it has not been clear whether the age-related decline in striatal function impairs initial goal-directed learning per se or simply prevents the updating of this learning in face of new environmental demands.
Further, this decline in behavioural flexibility was also accompanied by the deterioration of a specific pathway in the brain — called the parafascicular-to-cholinergic interneuron pathway (PF-to-CIN) — which resulted in faulty activation of striatal neurons. Disrupting this pathway in young mice reiterated the behavioural deficits observed in old mice, resulting in interference between old and new action-outcome associations. The findings show that the age-related decline in the PF-to-CIN pathway impairs the ability of mice to adjust to environmental changes in goal-directed learning tasks.
For the study, the team placed aged mice in a chamber and trained them to press two levers — one to receive a grain-based food reward and the other to receive a food pellet that was identical, except that it had a sweet taste. Then the mice were placed in another box, where they were given unrestricted access to only one of the pellets — grain-based pellets — for an hour. Immediately afterward, the mice were again placed in the original chamber and allowed to choose between the differently flavoured food pellets and both young and old mice preferred to eat the sweetened food pellets. The researchers next switched the associations, such that pressing lever one resulted in the delivery of sweetened food pellets, whereas lever two presses yielded grain-flavoured pellets.
Young mice successfully adjusted to this environmental change, pressing lever one to receive the sweetened food pellet after having gorged on the grain-based food pellets, and vice versa. However, old mice became confused and pressed the two levers at similar rates.