We describe a behavioral screen for the quantitative study of interval timing and interval memory in mice. Mice learn to switch from a short-latency feeding station to a long-latency station when the short latency has passed without a feeding. The psychometric function is the cumulative distribution of switch latencies. Its median measures timing accuracy and its interquartile interval measures timing precision. Next, using this behavioral paradigm, we have examined mice with a gene knockout of the receptor for gastrin-releasing peptide that show enhanced (i.e. prolonged) freezing in fear conditioning. We have tested the hypothesis that the mutants freeze longer because they are more uncertain than wild types about when to expect the electric shock. The knockouts however show normal accuracy and precision in timing, so we have rejected this alternative hypothesis. Last, we conduct the pharmacological validation of our behavioral screen using D-amphetamine and methamphetamine. We suggest including the analysis of interval timing and temporal memory in tests of genetically modified mice for learning and memory and argue that our paradigm allows this to be done simply and efficiently.

We investigated how the common measures of timing performance behaved in the course of training on the peak procedure in C3H mice. Following fixed interval (FI) pre-training, mice received 16 days of training in the peak procedure. The peak time and spread were derived from the average response rates while the start and stop times and their relative variability were derived from a single-trial analysis. Temporal precision (response spread) appeared to improve in the course of training. This apparent improvement in precision was, however, an averaging artifact; it was mediated by the staggered appearance of timed stops, rather than by the delayed occurrence of start times. Trial-bytrial analysis of the stop times for individual subjects revealed that stops appeared abruptly after three to five sessions and their timing did not change as training was prolonged. Start times and the precision of start and stop times were generally stable throughout training. Our results show that subjects do not gradually learn to time their start or stop of responding. Instead, they learn the duration of the FI, with robust temporal control over the start of the response; the control over the stop of response appears abruptly later.

Our results suggest that interval timing has potential as an assay for generalized cognitive performance and that the dopamine-clock hypothesis needs further refinement.