Patterns of behavioral entrainment in mice

Abstract

The experiments described in this Dissertation were designed to assess the process by which the master circadian clock in the suprachiasmatic nuclei (SCN) can be entrained by normocaloric scheduled feeding. Mouse lines that differ in some circadian rhythm characteristics and features of the SCN were used in these experiments. The initial experiment showed that the lines differ in the percentage of individuals that entrained to scheduled feeding. In mice that entrained to scheduled feeding, both wheel-running activity and the molecular clock in the SCN were synchronized to the time of food provision. The molecular clock in the SCN remained in phase with the free-running light entrainable activity component in mice that did not entrain to scheduled feeding. Subsequent experiments were performed to determine if line-specific differences in entrainment were related to differences in circadian rhythm characteristics. Several circadian characteristics showed line effects, but no differences between mice that entrained and those that did not entrain were found. The next series of experiments assessed the influence of non-photic factors not directly related to food availability and food ingestion. The results indicated that the timing of food availability relative to the phase of the SCN during the initial phase of the experiment, and factors related to disturbance, influenced entrainment. Three factors suggest involvement of the FEO in entrainment to scheduled feeding: 1) it is a circadian oscillator that is entrained by scheduled feeding; 2) entrained mice express robust food anticipatory behavior; and 3) the time of food provision corresponds to the peak of mPER2 expression in the SCN of entrained mice. The results of the disturbance experiments raise the possibility that the entrainment signal may be generated by a system other than the FEO, perhaps one related to arousal state or reward processes. Ultimately, multiple factors influencing entrainment of the SCN and SCN-controlled circadian rhythms by scheduled feeding are likely to be identified. These factors may include the combined influence of all non-photic signals received by the SCN, differences entrainment signal strength, and differences in the sensitivity or responsiveness of the clock mechanism due to genetic variation.