Abstract
Purpose: :
When placed in an environment with dark or light compartments, a mouse will choose to spend more time in the dark. The mechanisms controlling photophobia are not well understood, but may involve the convergence of visual and nociceptive information with associated emotional processing. Here we have sought to discover whether this response can be elicited by melanopsin photoreceptors, whether pupil constriction plays a role in this response, and to indicate which brain regions might be involved.
Methods: :
Photophobia was assessed in rodless coneless (rd/rd cl), wildtype, melanopsin knockout, (Opn4-/-) and mice lacking all functional photoreceptors (Opn4-/- Gnat1-/- Cnga3-/-). Assessment was made using an open field chamber, split into two halves comprising a dark chamber and an open area, which was either illuminated (~1500 lux white light) or remained dark in control experiments. The test duration was 30 minutes and the time spent in each compartment was monitored using TRUSCAN (Coulburn instruments US). Atropine drops (1%) were placed in the eyes of some animals prior to testing. Fos immuno-reactivity was used as an indicator of neural activity and was assessed in the brains of mice following 90 minutes of light or dark.
Results: :
Using this testing paradigm wildtype mice showed a strong preference for the dark compartment, as did the Opn4-/- mice. The rd/rd cl also spent significantly more time in the dark than in control (with the light off) experiments, but with a shorter duration than wildtypes. Mice lacking all photoreceptors did not show a preference for the dark compartment. Dilation of the pupil significantly increased the dark preference of rd/rd cl mice, increasing the duration to a similar level to that seen in wildtypes. In rd/rd cl mice, we found Fos immunoreactivity to be up-regulated by light in areas including the visual, retrosplenial and cingulate cortex.
Conclusions: :
Here we show that rods and/or cones and melanopsin cells are capable of mediating photophobia. We also report that in the rd/rd cl, melanopsin appears to signal to visual cortical regions and may access components of the limbic system.
Keywords: perception • photoreceptors: visual performance • pupil