Impaired behavioral suppression by light in metabotropic glutamate receptor subtype 6-deficient mice.

The metabotropic glutamate receptor subtype 6 is localized on the dendrites of ON bipolar cells in mammalian retina, and is responsible for synaptic transmission from photoreceptors to ON bipolar cells. We have previously provided electrophysiological evidence that metabotropic glutmate receptor subtype 6-deficient mice have an impairment in the ON visual pathway. In this study, we compared, between metabotropic glutamate receptor subtype 6-deficient (n=9) and wild-type mice (n=7), their daily wheel-running activity in constant dark and light-dark cycle environments. There was no difference in their free-running rhythmicity in a constant dark environment nor in their ability to entrain their active/rest phase to the phase-shifted light-dark cycle environment, indicating that the circadian system in mutant mice was functioning normally. However, the wheel-running activity was suppressed immediately after light onset of the light-dark cycle in wild-type mice (suppressive effect), whereas that of mutant mice was prolonged for several hours in spite of light onset (very weak suppressive effect). The suppression of activity in wild-type mice is a "masking effect" of the endogenous circadian rhythm in response to light stimuli. The results indicate that the failure of mutant mice to suppress their activity upon light onset is not due to abnormality in their circadian system, but to their lack of response to light stimuli. This study clearly demonstrates that the dysfunction of the ON visual pathway in metabotropic glutamate receptor subtype 6-deficient mice impairs their behavioral responsiveness to light and yet preserves their circadian system.