Multiple entrained oscillator model of food anticipatory circadian rhythms

Abstract

For many animal species, knowing when to look for food may be as important as knowing where to look. Rats and other species use a feeding-responsive circadian timing mechanism to anticipate, behaviorally and physiologically, a predictable daily feeding opportunity. How this mechanism for anticipating a daily meal accommodates more than one predictable mealtime is unclear. Rats were trained to press a lever for food, and then limited to one or more daily meals at fixed or systematically varying times of day. The rats were able to anticipate up to 4 of 4 daily meals at fixed times of day and two ‘daily’ meals recurring at 24 h and 26 h intervals. When deprived of food, in constant dark, lever pressing recurred for multiple cycles at expected mealtimes, consistent with the periodicity of the prior feeding schedule. Anticipation did not require the suprachiasmatic nucleus circadian pacemaker. The anticipation rhythms could be simulated using a Kuramoto model in which clusters of coupled oscillators entrain to specific mealtimes based on initial phase and intrinsic circadian periodicity. A flexibly coupled system of food-entrainable circadian oscillators endows rats with adaptive plasticity in daily programming of foraging activity.

Studying food entrainment: Models, methods, and musings

“…Despite these concerns, a side-by-side comparison of body temperature and FAA in mice on 60% CR vs. 3-h RF showed similar entrainment of activity and body temperature to feeding ( 57 ). Multiple feedings can also be employed: for example, Luby and colleagues demonstrated that mice can anticipate several meals per day but not with high precision while Petersen et al demonstrated that rats are much better at anticipation of multiple mealtimes ( 43 , 58 ).…”

“…Due to their increased size and complexity, many experiments have been completed in rats that would likely not be possible with mice. In a recent study, rats were taught to press a lever for food and then subjected to restricted food access, using lever pressing as a measure of FAA; the lever pressing showed a preprandial increase, even in animals with SCN lesions ( 43 ). Rats have also been shown to be more attuned to entrainment by palatable meals, developing FAA to the presence of a palatable treat provided in addition to standard chow ad libitum ( 44 , 45 ).…”

“…For example, we observed that higher ambient temperature is suppressive of FAA ( 66 ) while others have obtained robust inductions of FAA and other readouts of entrainment at thermoneutral temperatures in mice (29°C) ( 89 ). There are a variety of methods utilized for quantification of food entrainment, including but not limited to wheel running, lever pressing, telemetry sensors, photobeams, motion sensors, and video-based homecage behavior analysis ( 40 , 43 , 52 , 60 , 90 , 91 ). Direct comparison between telemetry sensors and motion sensors have shown that quantification through these methods are equivalent ( 92 ).…”

“…As we collect more examples of mutations and manipulations that lower FAA, it will be important to measure other aspects of entrainment and potential masking effects (i.e., studies under DD, for example). In the future, it will be important to move beyond activity alone (as measured by running wheels, photobeam breaks, or computer vision) and try to assay motivation to feed using instrumental behavior assays (nose-poking, lever pressing, etc) ( 43 ). If we find that all mice with reduced FAA also have reduced instrumental behavior then we can simply use activity, but we cannot make this correlation until we have more examples of animals lacking FAA.…”

Dopamine systems and biological rhythms: Let’s get a move on

“…Since there has been so much difficulty in isolating the neural constituent(s) of FAA, it has been suggested that such a region, referred to as a food entrainable oscillator (FEO), may not exist as a singular entity; therefore lesioning studies may be too narrow of an approach, and the molecular tagging or systems based approaches may offer higher potential in locating multiple FEOs distributed across the brain and body ( Davidson, 2009 ; Mistlberger, 2011 , 2020 ; Nishide et al, 2021 ). The ability of rodents to have multiple bouts of FAA entrained to multiple food deliveries with same or different cycle period further provided evidence that food entrainment is regulated by a multi-core network ( Petersen et al, 2022 ).…”