Extended Data Fig. 8 | Putative model for the circuit that drives circadian
food-anticipatory activity. Time-restricted access to food constitutes a
strong environmental cue that causes the alignment of the circadian system to
feeding schedules, driving food-anticipatory activity that precedes the
expected meal. The current view in the field is that a widespread system—
composed of elements referred to as food-entrainable oscillators (FEOs)—
controls the physiological and behavioural responses to TRF. Among the
candidates for FEOs are areas of the hypothalamus (such as the paraventricular
nucleus, ventromedial hypothalamic nucleus, dorsomedial hypothalamic
nucleus and arcuate nucleus), thalamic areas (such as the paraventricular
thalamus and the IGL), the brainstem (including the dorsal raphe nucleus and
parabrachial nucleus), other brain regions (such as the dorsal striatum,
infralimbic cortex, nucleus accumbens and cerebellum) as well as peripheral
targets (such as the gastrointestinal system). In this Article, we have delineated
a brain circuit (IGLNPY–SCN) that is critical for driving food-anticipatory activity
in adult mice. The functional assembly of this circuit requires innervation by
retinal ipRGCs to the SCN during a critical window. The proposed model
suggests crosstalk between an FEO (or FEOs) and the IGL, in which IGL neurons
act as a node of connection between the FEOs and the central pacemaker in the
SCN. Under TRF, inhibitory signals from IGLNPY neurons modulate the SCN
function, causing reduced firing activity, and therefore allowing signals from
the FEO (or FEOs) to drive robust food-anticipatory activity. The IGL could also
be part of the FEO (or FEOs), as previously suggested^7. IGLNPY neurons send
projections to several brain regions and, therefore, a role of any of these
non-SCN projections in modulating food-anticipatory activity should not be
excluded. How feeding-related stimuli modulate the FEO (or FEOs) and possibly
the IGL are unknown. Different humoral signals, such as ghrelin and insulin, are
strong candidates for modulating the FEO (or FEOs) and IGL.