Timing behavior in genetic murine models of neurological and psychiatric diseases

Abstract

How timing behavior is altered in different neurodevelopmental and neurodegenerative disorders is a contemporary research question. Genetic murine models (GMM) that offer high construct validity also serve as useful tools to investigate this question. But the literature on timing behavior of different GMMs largely remains to be consolidated. The current paper addresses this gap by reviewing studies that have been conducted with GMMs of neurodevelopmental (e.g. ADHD, schizophrenia, autism spectrum disorder), neurodegenerative disorders (e.g., Alzheimer's disease, Huntington's disease) as well as circadian and other mutant lines. The review focuses on those studies that specifically utilized the peak interval procedure to improve the comparability of findings both within and between different disease models. The reviewed studies revealed timing deficits that are characteristic of different disorders. Specifically, Huntington's disease models had weaker temporal control over the termination of their anticipatory responses, Alzheimer's disease models had earlier timed responses, schizophrenia models had weaker temporal control, circadian mutants had shifted timed responses consistent with shifts in the circadian periods. The differences in timing behavior were less consistent for other conditions such as attention deficit and hyperactivity disorder and mutations related to intellectual disability. We discuss the implications of these findings for the neural basis of an internal stopwatch. Finally, we make methodological recommendations for future research for improving the comparability of the timing behavior across different murine models.