The components of a circadian clock are the input, pacemaker, and output. The input of the self-sustaining<unk> ,<unk> , is<unk>  and the output is<unk>  anticipatory activity (FAA). This activity is correlated with an increase in an organism’s activity leading up to feeding time. The FAA is present in constant conditions such as fasting/time-restricted feeding, and it synchronizes to<unk>  that is presented in time intervals that follow a circadian (24 hour) rhythm. Time-restricted feeding is when all of the caloric intake for a day is limited to certain times of the day. A frequent circadian timekeeping mechanism involves CLOCK/BMAL genes, cryptochrome/period genes, and a transcription/translation feedback loop (TTFL) operating in the suprachiasmatic nucleus (SCN). Clock genes are transcribed and translated into a protein product, and this protein accumulates and inhibits the promoter of the clock genes from initiating transcription. However, CLOCK mutant, cryptochrome (Cry) knockout, period (Per) knockout, and SCN knockout mice all had FAA present, so the<unk>  appears to not operate through the traditional circadian timekeeping mechanism. Circadian genes Studies have shown that Per1, Per2, and Per3 knockout mice continue to have robust FAA; these genes are not necessary for<unk><unk> y activity. Research into Bmal1 knockout mice has been more mixed, but many studies have concluded that FAA can be achieved without the Bmal1 gene. Cry1, Cry2, and NPAS2 (Clock gene paralog) knockout mice also show FAA activity, so none of these are necessary for the<unk> . Still, these circadian genes have a modulatory effect on<unk>  activity. Mice that have their Per1/Per2/Per3 genes knocked out have<unk>  rhythms with shortened periods, and the same is true for Cry1 knockout mice. Cry2 knockout mice have longer periods for their<unk>  rhythms. Thus, the Per and Cry genes are involved but not necessary for<unk>  timekeeping. NPAS2 knockout mice show delayed expression of FAA, so it affects the input/output of FAA or the<unk>  timekeeping itself. The studies that looked at these knockout mice were conducted by Pitts et al., Iijima et al., and Pendergast et. al. Yet, clock gene expression drastically increases in the dorsomedial hypothalamic nuclei (DMH) during restricted feeding, and this expression continues without feeding, indicating the circadian<unk> y activity of the<unk> . Thus, it is likely that traditional clock genes are heavily involved or necessary for the<unk> . This is still not resolved. Neurotransmitter signaling Out of the researched neurotransmitters, only disrupting the dopamine signaling pathway appears to disrupt normal FAA. It is postulated that the<unk>  may be in the dopaminergic circuitry. Mice without a functional Dopamine D1 receptor have attenuated FAA. Mice that are given a D1 receptor agonist show FAA without restricted feeding (a condition required for it otherwise). Thus, the dopamine pathway regulates the FAA, but it is unclear if it impacts the input, pacemaker, or output portion of the<unk>  pathway. Hormone and neuropeptide signaling Hormones involved with the regulation of<unk>  intake have been investigated for their role in the<unk>  timekeeping mechanism. Leptin, a hormone that suppresses<unk>  intake, is not required for FAA, but it influences the extent of FAA. Ghrelin, a hormone that increases in the plasma leading up to mealtime and activates the dopaminergic pathway, also has a modulatory effect on FAA but is not necessary for it. The signaling pathways of leptin and ghrelin lead to the hypothalamus’ melanocortin system, and research into this system has also shown that it modulates, but is not necessary for, FAA. The neuropeptides, Orexin A and B, stimulate<unk>  intake, and they have a modulatory effect on FAA but are not necessary for it. Neuropeptide Y also stimulates<unk>  intake and increases expression prior to restricted feeding, but it has not been found to affect FAA. Proteins involved in the SCN pathway (Prokineticin 2 (PK2), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP)) do not influence the FAA. Sirtuin 1(Sirt1) regulates physiological responses to<unk>  intake, and appears to modulate, but not be necessary for FAA. RGS16, a gene regulating G-protein coupled receptor signaling, attenuates FAA but is also not necessary for it.
Food-entrainable oscillator
Tetanic contraction
High-conductance state
Parafunctional activity
Optokinetic response
Circadian rhythm
Vagovagal reflex
Junctional rhythm