Spaced Training Can Improve Learning in Down, Angelman Patients, Mouse Study Shows

Spaced training interventions may be used to minimize learning impairments associated with neurological disorders, including Down and Angelman syndrome, a mouse study has found.

The results, “Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities,” were published in Translational Psychiatry.

In psychology it is widely recognized that repeated training sessions spaced in intervals are better for learning than one long, isolated training session. Nevertheless, very few studies have put this concept to the test in the context of neurological disorders characterized by deep cognitive and learning impairments.

“There is, however, a report suggesting that cue sampling at one-hour intervals significantly reduces the learning impairment found in [a mouse] model of Fragile X syndrome,” the researchers stated.

In this study, researchers from the University of California Irvine set out to test whether exposing a mouse model of Angelman (Ube3a mice) and Down syndrome (Ts65Dn trisomy mice) to spaced training sessions would improve their learning capabilities.

To test their hypothesis, researchers devised a training session plan in which animals had to perform four learning and memory tasks at one-hour intervals:

• Object location memory task, in which animals were trained to identify a particular object and then were placed in a chamber with two objects — a new and the familiar object they had been trained to recognize — and had to recall and select the familiar object (assessed by measuring the amount of time animals spent inspecting both objects);
• Novel object recognition task, in which animals were placed in an arena with two objects — an object identical to others previously seen and a new object — and had to spend more time investigating the new object instead of the identical one to which they had already been exposed;
• Water maze spatial learning task, in which animals had to memorize the location of a platform to avoid swimming for long period of time inside a circular pool;
• Rotarod motor learning task, in which animals had to learn to adjust their balance and speed while running on a moving rod without falling.

Results showed that mice with Down syndrome that had been trained with spaced sessions had better performance on the object location, novel object recognition, and water maze tasks, compared with animals that had not been trained with spaced sessions.

Likewise, spaced training also improved the performance of mice with Angelman syndrome on the water maze spatial learning task. However, it did not improve their motor learning during the rotarod task.

“Rotarod motor learning is mediated primarily by the cerebellum, while acquisition in the water maze, object location, and novel object recognition paradigms are heavily dependent upon structures in the cortical telencephalon. It is reasonable to expect that memory [involving different regions of the brain may respond differently to spaced training],” the researchers explained.

The cerebellum is a brain region responsible for body balance; the telencephalon is the largest portion of the brain that participates in most cognitive tasks.

“The present findings in the Ts65Dn trisomy mouse model of Down syndrome and the Ube3a … mouse model of Angelman syndrome, along with our previous parallel findings in the Fmr1 mutant mouse model of Fragile X syndrome, support the strategy of therapeutic behavioral interventions using spaced sessions of distributed learning opportunities, to enhance cognitive abilities in neurodevelopmental disorders characterized by intellectual disabilities,” the researchers concluded.