Figure 2. Retinal and brain circuits underlying the effects of light on non-image forming visual functions.

A. Schematic view of the retina showing the organization of different neuronal populations and their synaptic connections. Rods and cones are confined to the photoreceptor layer. Light detected by rods and cones is processed and signaled to retinal ganglion cells (RGCs) through horizontal, amacrine and bipolar cells. RGCs are the only output neurons from the retina to the brain. A subset of RGCs (2–5% of the total number of RCGs) are intrinisically photosensitive RGCs (ipRGCs). There are at least 5 subtypes of ipRGCs (M1–M5) with different morphological and electrophysiological properties, which show widespread projection patterns throughout the brain.

B. ipRGCs project to numerous brain regions, including many that have a role in driving light-mediated behaviors, including circadian photoentrainment and sleep. In addition, ipRGCs also innervate nuclei involved in depression and/or anxiety, such as the MA, LHb and SPZ (highlighted in green) indicating a possible direct role of light on mood.

C. Several of the ipRGCs targets (blue), including the SPZ, VLPO, LH and LHb also receive innervation from the SCN, raising the possibility that in addition to its pacemaker function, the SCN can also act as a conduit for light information. Interestingly, the MA and the LHb are also brain peripheral clocks that receive direct retinal innervation. Areas involved in mood regulation (VTA and raphe) and cognition (LH) can be influenced by light either via the SCN or in parallel via the MA and LHb.

LHb: lateral habenula; MA: medial amygdala; SCN: suprachiasmatic nucleus; SPZ: subparaventricular zone; VLPO: ventrolateral preoptic area; VTA: ventral tegmental area; HC: hippocampus; LH: lateral hypothalamus; LC: locus coeruleus.