Neural Mechanisms of Food-Anticipatory Circadian Rhythms in Rats

Circadian rhythms of behavior and physiology in rodents are regulated by a system of endogenous circadian oscillators synchronized to the external environment by two distinct pacemakers that are mutually coupled under normal conditions. The suprachiasmatic nucleus (SCN) is the master light-entrainable pacemaker (LEP) that mediates synchrony to the day-night cycle. The second pacemaker is a food-entrainable pacemaker (FEP) and has yet to be identified, but is capable of synchronizing circadian rhythms to restricted feeding (RF) schedules independent of the SCN. Rat, hamster and mouse behavior and physiology entrains to RF despite complete SCN ablations. The studies that comprise this dissertation examine two candidate FEP structures: the thalamic paraventricular nucleus (PVT); and the dorsomedial hypothalamus (DMH). Both the PVT and DMH are promising targets given evidence suggesting they: 1) are active in anticipation of the feeding window (as described in glucose metabolism and c-fos imaging studies); 2) are involved in arousal, ingestive behavior, and visceral function; 3) have reciprocal connections with the SCN which could mediate proposed coupling between the LEP and FEP under normal conditions; and 4) have been implicated in prior lesion studies, whereby damage to these structures has been shown to attenuate food-anticipatory physiology or behavior. To determine whether the PVT or DMH are critical for the expression of food-entrainable circadian rhythms, in separate studies rats received unambiguously complete radiofrequency lesions of the target structures. PVT-lesioned rats as well as DMH-lesioned rats are essentially indistinguishable from intact controls in terms of their capacity to entrain to and anticipate RF schedules. These results indicate that neither the PVT, nor the DMH are necessary for circadian food entrainment and thus they can be ruled out as candidate FEP structures. A series of follow-up studies were conducted to identify and explain the reasons why the DMH lesion results described above were contrary to earlier reports that the DMH was critical for expression of food-entrainable circadian rhythms.