Research reportIncreased masking response to light after ablation of the visual cortex in mice
Introduction
Behavior and physiology are synchronized to the 24-h day by distinctive responses to light. First, light synchronizes a circadian clock in the hypothalamus which in turn drives most daily rhythms such as the sleep–wake cycle. This effect of light on the circadian clock is slow and requires protein synthesis [24]. Second, light can have a fast and direct effect on rhythmic variables. In a nocturnal rodent, for example, light at night causes an immediate reduction of wheel running. This fast effect of light on rhythmic variables is referred to as masking, because it masks or obscures control by the circadian clock (see [15] for terminology). Both processes, masking and entrainment, require only detection of irradiance, and may both be mediated by the same novel photoreceptors. This can be concluded from studies with mutant and transgenic mice which lack both rods and cones. These mice entrain normally to light–dark cycles and they also suppress their locomotor activity to light pulses [18], even though they must be considered blind. The irradiance detection system mediating both entrainment of circadian rhythms and masking is thought to start with photoreceptive cells in the inner retina. Melanopsin has been proposed recently as a candidate for the photopigment mediating these responses [5].
Although irradiance detection without rod and cone photoreceptors is sufficient for masking to occur, several observations indicate that the classical rod and cone system, in addition to its task in image formation, may also influence masking of locomotor activity. An enhanced masking response, that is, greater inhibition of activity by light of a given strength, has been seen with several different types of retinal degeneration. It has been found in two strains of rd/rd (retinally degenerate) mutant mice, which loose nearly all their rods and cones [16], in rds/rds (retinally degenerate slow) mice old enough for the degeneration to be advanced [Mrosovsky, unpublished], and in transgenic mice with degeneration induced by a diphtheria toxin gene fused to a rod promoter [17]. Greater clock resetting after a light pulse has been also found in this strain of transgenic mice [9]. In addition, enhanced masking to light can occur after lesions of the thalamic intergeniculate leaflet (IGL) [23] or the dorsal lateral geniculate of the thalamus (dLGN) [3].
These results indicated that if input to the visual cortex, or possibly other visual centers past the geniculate, is interrupted, the suppression of locomotor activity by light was unimpaired and even enhanced. The results were similar whether visual input to the cortex was interrupted at the retinal level (in case of the various retinal degenerations) or along the visual pathway to the cortex (dLGN lesions). The enhanced masking seen after lesions of the IGL was therefore probably also the result of interruption of visual input to the cortex, as the IGL lesioning procedure undoubtedly resulted in accidental damage to the adjacent dLGN, which is very difficult to avoid because of the anatomical location of the IGL [20]. Although these studies suggested that deprivation of visual input to the cortex is causing the enhanced masking, the possibility remained that other areas receiving retinal input may have been responsible, such as the superior colliculus, a structure generally thought to be involved in visual reflexes.
The present experiments aimed to substantiate the assumption that deprivation of input to the visual cortex results in enhanced masking. We therefore tested how removal of the visual cortex affected masking of locomotor activity in mice. We also assessed the effects of combined lesions of the visual cortex and superior colliculus because the superior colliculus is a major projection area of the visual system in rodents.
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Animals, housing, and experimental procedure
Seventy-three male C57BL/6JICO mice, aged 7.5±0.5 weeks, were obtained from IFFA Credo (L’Arbresle, France). They were housed in the INSERM laboratory at Bron, in groups in cages approx. 75×50×25 cm, and fed chow with apple supplements. The room where the mice were kept had windows; temperature was ∼25 °C.
One group of mice (n=30) received visual cortex lesions, a second group (n=22) had their visual cortex ablated and in addition visual input to the superior colliculi was severed. A further
Description of lesions
The mice in the visual cortex group had 83.1% (±6.4 S.E.; n=6) and the group with additional SC lesions had 87.0% (±5.9 S.E.; n=6) of their visual cortex ablated. In mice with visual cortex lesions 13.7% (±3.4 S.E.) and in the mice with additional SC lesions 12.2% (±1.8 S.E.) of the cortex surface area outside the visual cortex was damaged (see Fig. 1). Mice with sham lesions (n=15) had intact cortices. In mice with visual cortex lesions only, slight additional damage to one side of the SC was
Discussion
The results demonstrate that mice with visual cortex lesions or combined visual cortex and superior colliculus lesion showed a stronger reduction of their wheel running to light pulses than did sham-operated animals. This finding supports the view that the visual cortex influences the suppression of locomotor activity by light through a yet unidentified pathway.
Even though our lesion estimates based on brain atlas coordinates indicate that the visual cortex was not completely removed in all
Acknowledgements
We thank Naura Chounlamountri, Peggy Salmon, Eckard Glockmann, Natalie Chung and Sonja Banjanin for help. Support came from the Canadian Institutes of Health Research and a grant from Biomed2 (BMH4-CT972327). These experiments comply with the Guidelines of the Canadian Council on Animal Care.
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