Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice.

Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key elements from the ECG waveform (RR-, PR-, ST-, QT-interval, QT corrected, and QRS complex) demonstrate minimal sexual dimorphism. As expected, anesthesia induces a decrease in heart rate and was shown for both inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. In the absence of pharmacological, environmental, or genetic challenges, we did not observe major age-related ECG changes in C57BL/6N-inbred mice as the differences in the reference ranges of 12-week-old compared to 62-week-old mice were negligible. The generalizability of the C57BL/6N substrain reference ranges was demonstrated by comparison with ECG data from a wide range of non-IMPC studies. The close overlap in data from a wide range of mouse strains suggests that the C57BL/6N-based reference ranges can be used as a robust and comprehensive indicator of normality. We report a unique ECG reference resource of fundamental importance for any experimental study of cardiac function in mice.

The emergence of temporal hyperacuity from widely tuned cell populations.

Typically, individual neural cells operate on a millisecond time scale yet behaviorally animals reveal sub-microsecond acuity. Our model resolves this huge discrepancy by using populations of many widely tuned cells to attain sub-microsecond resolution in a temporal discrimination task. An echolocating bat uses its auditory system to locate objects and it demonstrates remarkable temporal precision in psychophysical tasks. Auditory cells were simulated using realistic parameters and connected in three ascending layers with descending projections from auditory cortex. Coincidence detection of firing collicular cells at thalamus and subsequent integration of multiple inputs at cortex, produce an estimate of time represented as the mean of the active cortical population. Multiple estimates allow the model bat to use memory to recognize predictable change in stimuli values. The best performance is produced using cortical feedback and a computation of target time based on combining the current and previous estimates. Temporal hyperacuity is attained through population coding of physiologically realistic cells but depends on the inherent properties of the psychophysical task.