Mice can be shown to process temporal information as if they use an internal stopwatch that can be run, stopped, and reset on command and whose speed of “ticking” is adjustable. In addition, interval-timing behavior can be separated into clock, memory, and decision stages of information processing such that one stage can be modified without changing the others. In order to demonstrate the efficacy of interval-timing procedures in the evaluation of behavioral phenotypes, proline transporter (PROT) deficient mice (+/+, +/-, and -/-) were assessed for motor control (Rotarod beam), spatial memory (Morris water-maze), and temporal generalization (peak-interval procedure) competency. The findings demonstrate that interval-timing procedures can be profitably integrated into a behavioral battery and used to selectively diagnose the psychological abnormalities associated with transgenic, knock-out, and knock-down mouse models of human diseases.

Our laboratory has discovered that alterations in choline availability to the developing rat fetus lead to long-term changes in spatial and temporal memory function across the lifespan and associated changes in the septo-hippocamal system. The current study was undertaken to determine if performance on an attention task, believed to be relatively independent of septo-hippocampal function, was modified by changes in choline availability prior to birth. A sustained attention task was developed for mice that includes all the features of the 2-choice signal-detection procedure initially applied to rats (McGaughy & Sarter, 1995). Prenatal choline deficiency significantly impaired the ability of adult mice to sustain attention to a brief visual cue throughout a session as evidenced by decreased “Hits” and increased “Omissions” during the second-half of trials. In contrast, prenatal choline supplementation enhanced the ability of mice to detect visual cues but did not alter their ability to maintain attention throughout a session. These data support the view that the effects of alterations in choline availability on brain anatomy, physiology, and function likely extend beyond the septo-hippocampal system that modulates spatial memory. In the case of the sustained attention task, this likely includes cholinergic projections from the basal forebrain to neocortex.

The hypothesis that the standard acoustic startle response (ASR) paradigm contains the elements of interval timing was tested. Acoustic startle stimuli were presented at a 10-s interstimulus interval (ISI) for 100 trials leading to habituation of the ASR. The ISI was then changed to either a shorter (5-s) or a longer (15-s) duration using a betweensubjects design. Dishabituation of the ASR was used to measure the degree of temporal generalization for the interval-timing process. The ASR showed dishabituation at both shorter and longer ISI values on the first trial following the change in ISI. The dishabituation resulting from the change in ISI was temporary and the ASR rapidly returned to levels of response habituation showing rate sensitivity to the frequency of stimulus presentation. Interval timing may be a standard feature of this habituation paradigm, it serves to anticipate the time of occurrence of the subsequent stimulus and to prepare the startle response, and provides a computational dimension lacking in the habituation process per se.