Scopolamine induced learning deficit in marmosets

Abstract

In monkeys, the muscarinic cholinergic receptor antagonist scopolamine is known to broadly disrupt learned behaviors, though the precise nature of the cognitive deficits has been questioned. Experimentally observable deficits in memory can be ascribed to poor attentional focusing, human interference as well as age, sex, and dosing regimen. Stress and social isolation can also play a role during behavioral testing, particularly in small nonhuman social primates like marmosets that have been used widely. In this study, we examine the effects of scopolamine in marmosets under conditions of reduced stress, attentional distraction, and human interference. Using a custom designed home-cage touchscreen-based testing system, we investigated the influence of scopolamine on the performance on a visual associative learning task. During self-paced, voluntary testing, monkeys learned to discriminate pairs of complex visual patterns through trial and error by touching the stimulus associated with reward. Using this approach, we demonstrated over 75% discrimination accuracy in the eight marmosets tested (male and female) within three days of home-cage testing. Although the averaged data revealed no impact of acute or chronic scopolamine injections on learning, modeling the choice data with trial-level analysis revealed both age- and sex-specific deficits. The results demonstrate the value of home-cage testing combined with trial-level analysis to reveal subtle behavioral changes, such as those brought about by scopolamine. Significance statementWe created a custom home cage testing system to test the effects of muscarinic cholinergic blockade on complex discrimination learning in marmoset monkeys. We found that systemic scopolamine administration disrupts visual association learning in a manner that was specific to older females. This deficit was hidden in session-averaged measures and only became evident in trial-level modeling of the choice data. Our findings demonstrate that cholinergic blockade impairs the dynamics of learning in marmosets and highlights the value of trial-level analysis for detecting nuanced pharmacological effects on primate cognition.