Light and the laboratory mouse

Abstract

Light exerts widespread effects on physiology and behaviour. As well as the widely-appreciated role of light in vision, light also plays a critical role in many non-visual responses, including regulating circadian rhythms, sleep, pupil constriction, heart rate, hormone release and learning and memory. In mammals, responses to light are all mediated via retinal photoreceptors, including the classical rods and cones involved in vision as well as the recently identified melanopsin-expressing photoreceptive retinal ganglion cells (pRGCs). Understanding the effects of light on the laboratory mouse therefore depends upon an appreciation of the physiology of these retinal photoreceptors, including their differing sens itivities to absolute light levels and wavelengths. The signals from these photoreceptors are often integrated, with different responses involving distinct retinal projections, making generalisations challenging. Furthermore, many commonly used laboratory mouse strains carry mutations that affect visual or non-visual physiology, ranging from inherited retinal degeneration to genetic differences in sleep and circadian rhythms. Here we provide an overview of the visual and non-visual systems before discussing practical considerations for the use of light for researchers and animal facility staff working with laboratory mice.

Keywords: Circadian; Retina; Wavelength; Welfare.

Fig. 1

The mouse eye and retina. A) The mouse eye is similar in structure to that of most other vertebrates, although the lens is relatively larger. B) The retina is a layered structure and light must pass through the inner retinal layers to reach the light sensitive photoreceptors in the outer retina. The retina contains two classes of visual photoreceptor, rods which mediate low light (scotopic) vision and cones which mediate bright light (photopic) vision and provide colour vision. Mice have two cone visual pigments, an ultraviolet light sensitive (UVS) opsin and a middle-wavelength sensitive (MWS) opsin. However, in 95% of cones, these opsins are co-expressed. In addition to the rods and cones, a subset of melanopsin-expressing photosensitive retinal ganglion cells (pRGCs) have recently been identified, mediating many non-visual responses to light.

Fig. 2

Spectral sensitivity of human and mouse visual pigments. The human and mouse retina contain a different complement of light-sensitive visual pigments. A) The human retina contains rods and three cone classes, maximally sensitive to red, green and blue light. B) By contrast, the mouse retina is rod dominated (97% of photoreceptors) and contains cone opsins maximally sensitive to ultraviolet and green light. As a result, mice are relatively less sensitive to long wavelength light. For example, at 600 nm (red light), the human visual system is 12 times more sensitive than the mouse visual system. As such, whilst mice are less sensitive to red light, care must be taken to ensure that such stimuli are as dim as possible to allow researchers and animal facility staff to operate. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Interaction between rods, cones and melanopsin pRGCs. A) Rods and cones provide input to melanopsin pRGCs. Note that most cones co-express UVS and MWS opsin. Rod input is via AII amacrine cells. B) The mammalian retina functions over a very wide range of light intensities. Rods mediate responses under low light (scotopic) conditions, and as light levels increase cones and then melanopsin may contribute as rods become saturated. As an approximation, 1 lx of white light will be equivalent to roughly 12 log quanta, depending on the spectral power distribution of the light source. Figures based on (Lucas et al., 2014) (A) and (Dacey et al., 2005) (B).

Fig. 4

Summary of mouse visual and non-visual responses to light. Light detected by the retina is transmitted to the lateral geniculate nucleus (LGN) from which it is relayed to the visual cortex to mediate visual responses. By contrast, projections via the retinohypothalamic tract to the suprachiasmatic nuclei (SCN) mediate entrainment of circadian rhythms to light. Projections from melanopsin pRGCs to the olivary pretectal nucleus (OPN) mediate pupillary light responses, whereas projections to the ventrolateral preoptic nuclei (VLPO) modulate sleep. The superior colliculus (SC) receive input from both visual and non-visual pathways to direct attention to visual stimuli. Figure based upon (Hattar et al., 2006).