How Does Light Regulate Mood and Behavioral State?

Abstract

The idea that light affects mood and behavioral state is not new. However, not much is known about the particular mechanisms and circuits involved. To fully understand these, we need to know what properties of light are important for mediating changes in mood as well as what photoreceptors and pathways are responsible. Increasing evidence from both human and animal studies imply that a specialized class of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs), plays an important role in the light-regulated effects on mood and behavioral state, which is in line with their well-established roles in other non-visual responses (pupillary light reflex and circadian photoentrainment). This paper reviews our current understanding on the mechanisms and paths by which the light information modulates behavioral state and mood.

Keywords: alertness; behavioiral state; depression; ipRGCs; light; mood; non-visual responses.

Figure 1

Relative sensitivity curves for all of the opsins present in the mouse (A) and human (B) retina. Note the limitation of using blue light (~470 nm) to excite melanopsin only (λ_max~480 nm); although there is significant overlap with the melanopsin peak sensitivity, this light also excites other photoreceptors to different extents.

Figure 2

ipRGC pathways for mood regulation in mice. (A) Schematic presentation of mammalian retina, with six subtypes of ipRGCs (M1–M6). (B) Brain areas involved in the regulation of mood and behavioral state were shown to have increased activity (measured upregulation of c-Fos, an early marker of neural activation) following the acute activation of ipRGCs using chemogenetics (ipRGCs expressing Gq-coupled chemogenetic hM3Dq receptor, depicted by a red star), in pink. Nuclei labelled in blue showed no c-Fos increase. Figure adapted from [63]. (C) Two identified pathways by which ipRGCs are involved in light-induced regulation of depressive-like behavior. The M1 Brn3b+ ipRGCs project directly to PHb (perihabenular nucleus) and are involved in depressive-like behaviors in mice triggered by chronic aberrant light exposure (T7 cycle). M4 ipRGCs innervate the vLGN/IGL-LHb (ventral lateral geniculate nucleus/intergeniculate leaflet-lateral habenula) pathway and are responsible for short-term light effects in decreasing depressive-like behavior. (D) Nuclei involved in the regulation of mood and behavioral state that receive direct projections from ipRGCs. Paraventrical hypothalamic nucleus (PVN), the dorsomedial hypothalamus (DMH), lateral hypothalamus (LH), ventrolateral preoptic nucleus (VLPO); amygdala (Amg), intralaminar thalamic nuclei (ITL), paraventricular thalamus (PVT), lateral habenula (LHb), nucleus accumbens (NAc), Bed nucleus of the stria terminalis (BNST) and periaqueductal gray (PAG).