Not All Mice Are Created Equal: Interval Timing Accuracy and Scalar Timing in 129, Swiss-Webster, and C57Bl/6 Mice

Many species, including humans, show both accurate timing-appropriate time estimation in the seconds to minutes range-and scalar timing-time estimation error varies linearly with estimated duration. Behavioral paradigms aimed at investigating interval timing are expected to evaluate these dissociable characteristics of timing. However, when evaluating interval timing in models of neuropsychiatric disease, researchers are confronted with a lack of adequate studies about the parent (background) strains, since accuracy and scalar timing have only been demonstrated for the C57Bl/6 strain of mice (Buhusi et al., 2009). We used a peak-interval procedure with three intervals-a protocol in which other species, including humans, demonstrate accurate, scalar timing-to evaluate timing accuracy and scalar timing in three strains of mice frequently used in genetic and behavioral studies: 129, Swiss-Webster, and C57Bl/6. C57Bl/6 mice showed accurate, scalar timing, while 129 and Swiss-Webster mice showed departures from accuracy and/or scalar timing. Results suggest that the genetic background / strain of the mouse is a critical variable for studies investigating interval timing in genetically-engineered mice. Our study validates the PI procedure with multiple intervals as a proper technique, and the C57Bl/6 strain as the most suitable genetic background to date for behavioral investigations of interval timing in genetically engineered mice modeling human disorders. In contrast, studies using mice in 129, Swiss-Webster, or mixed-background strains should be interpreted with caution, and thorough investigations of accuracy and scalar timing should be conducted before a less studied strain of mouse is considered for use in timing studies.