Mouse Model for Angelman Reveals Touchscreen Learning Deficits

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A mouse model for Angelman and Down syndrome has revealed deficits in touchscreen learning, suggesting that assessing this type of outcome may help identify effective therapies.

The study, “Touchscreen learning deficits in Ube3a, Ts65Dn and Mecp2 mouse models of neurodevelopmental disorders with intellectual disabilities,” appeared in the journal Genes, Brain and Behavior.

The defects underlying genetic diseases characterized by intellectual impairments, such as Angelman’s and Down syndrome, often lead to additional loss of motor and sensory skills. This precludes researchers from using standard cognitive tests.

“Touchscreen learning and memory tasks in small operant chambers have the potential to circumvent these confounds,” wrote researchers at the University of California Davis School of Medicine in Sacramento.

Researchers used touchscreen visual discrimination learning to evaluate the performance of a mouse model of Angelman and two other animal models for Down and Rett syndromes. They also tested mice for learning and memory skills (with the Morris water maze), motor coordination and balance (with the rotarod test) and locomotion (with the open field test).

The results revealed that Angelman and Down syndrome mouse models had cognitive deficits on a two-choice visual discrimination assay — a task that involves knowing the difference between two shapes displayed simultaneously on a screen where one is correct and is associated with a reward, and the other is incorrect and is punished with a timeout.

Researchers observed that mice models of Angelman and Down syndrome learned touchscreen visual discrimination at a significantly slower rate. Both showed deficits in performing in the water maze, reinforcing “evidence in the literature that spatial learning is impaired in genetic mouse models of Angelman and Down syndrome,” they wrote.

These animals also had difficulties in motor coordination and balance, confirming previous reports. Yet researchers saw no differences in locomotion between mutated mice and their healthy controls.

Since the performance on the touchscreen test requires minimal locomotion, coordination and balance, the deficits seen in these parameters in both Angelman and Down syndrome mice are not the cause for the cognitive deficits detected on visual discrimination learning.

“Robust acquisition deficits in touchscreen assays offer new preclinical outcome measures for discovering effective therapeutics for neurodevelopmental disorders with intellectual disabilities such as Angelman and Down syndromes,” authors concluded.