FIGURE 2.

The VTA and NAc are integrated into the circadian system through indirect SCN input. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus receives photic information from intrinsically photosensitive retinal ganglion cells (ipRGCs) in the retina via the retinohypothalamic tract (RHT). While the SCN generates rhythms through its highly coupled network of neuronal and glial oscillators, the SCN rhythms are entrained to environmental light/dark cycles by retinal photic information. The SCN synchronizes extra-SCN oscillators throughout the organism, both centrally and peripherally, via autonomic, metabolic, and hormonal signals. These extra-SCN oscillators are thought to afford local temporal control of complex physiology and behaviors. In particular, the ventral tegmental area (VTA) and nucleus accumbens (NAc) of the mesolimbic pathway may receive and integrate circadian information through indirect connections with the SCN. In addition to reciprocally communicating with the NAc through direct and indirect projections to mediate reward, the VTA may receive indirect SCN circadian input via the lateral habenula (LHb) and/or the medial preoptic area (mPOA)—both of which are direct outputs of the SCN and also receive photic information from ipRGC innervation. Notably, the VTA has also been shown to directly innervate the SCN and regulate photoentrainment. The NAc may receive indirect SCN circadian input via the paraventricular nucleus of the thalamus (PVT), one of the densest extrahypothalamic outputs of the SCN, or via the VTA. Schematic illustrates a sagittal section of a rodent brain. Undefined: olfactory bulb (Ob); cerebellum (Cb); See key for more details. Figure created with BioRender.com.