Synaptic plasticity in CNGA3(-/-) mice: cone bipolar cells react on the missing cone input and form ectopic synapses with rods.

In the mammalian retina, rods and cones connect to distinct sets of bipolar cells. Rods are presynaptic to a single type of rod bipolar cell, whereas cones connect to different types of cone bipolar cells. Synaptic rewiring between cone photoreceptor terminals and rod bipolar cell dendrites has been described as a general result of photoreceptor degeneration. To investigate whether cone bipolar cells also show synaptic plasticity in the absence of cone input, we studied the connectivity of cone bipolar cell dendrites in CNGA3(-/-) mice, a model with specific loss of cone photoreceptor function. Dendritic connections of ON and OFF cone bipolar cells were visualized using specific cell markers or by intracellular injection with fluorescent dyes. The results show that cone bipolar cells in CNGA3(-/-) mice form ectopic synapses with rods. In contrast, cone bipolar cells do not form ectopic synapses with rods in CNGA3(-/-)Rho(-/-) mice, in which both types of photoreceptors are nonfunctional. In analogy with these results, we found that input-deprived rod bipolar cells form ectopic synapses with functional cones in Rho(-/-) mice but not with inoperable cones in the CNGA3(-/-)Rho(-/-) mouse. Our data indicate that the formation of ectopic bipolar cell synapses in the outer plexiform layer requires a functional presynaptic photoreceptor.

Morphological characterization of the retina of the CNGA3(-/-)Rho(-/-) mutant mouse lacking functional cones and rods.

PURPOSE: To assess the structural changes in the retina caused by a functional blockade of rods and cones and to document the time course of their degeneration. METHODS: Double knockout mice were generated by cross-breeding CNGA3(-/-) mice with Rho(-/-) mice. Retinas of mutant and wild-type mice from 3 weeks up to 12 months of age were studied by confocal light and electron microscopy. The retinas were immunostained with cell-type-specific markers and with antibodies against synapse-associated proteins and transmitter receptors. RESULTS: In 3-week-old CNGA3(-/-)Rho(-/-) mice, retinal layers showed normal structural organization, and photoreceptors established normal synaptic contacts. Until postnatal week (Pw)7, presynaptic markers and postsynaptic glutamate receptors were well expressed at the photoreceptor terminals. Photoreceptor degeneration started at Pw4, progressing to an almost complete loss by 3 months. Rod spherules showed an increase in the number of synaptic ribbons and postsynaptic elements during this early stage of degeneration, and horizontal cell processes grew into the outer nuclear layer. At later stages of retinal degeneration, the inner plexiform layer (IPL) was also affected. Rod bipolar cell axon terminals showed morphologic alterations, but the stratification pattern of cone bipolar cell axons and amacrine cell processes appeared unaffected. Transmitter receptors (GlyRalpha3, GABA(A) alpha2, GluR2/3) showed no obvious changes in the distribution and density of their synaptic clusters throughout the IPL at postnatal month 12. CONCLUSIONS: The normal structural and synaptic organization of the mutant retina at Pw3 suggests that photoreceptor light responses are not essential for the development of the retinal circuitry. However, functional photoreceptors are necessary for the maintenance of rods and cones and their contacts in the OPL, because they degenerate almost completely by 3 months after birth. Degenerative changes can also be observed in the IPL; however, they appear to have a slower time course and by 12 months of age the IPL circuitry appears to be surprisingly intact.

Anti-gay sentiment among adolescents in Belgium and Canada: a comparative investigation into the role of gender and religion.

Previous research has indicated that opposition toward lesbian, gay, bisexual, and trangender (LGBT) rights remains prevalent among Western populations. In this article, we investigate the determinants of anti-gay attitudes among adolescents in two liberal democracies, Belgium (n = 6,330) and Canada (n = 3,334). The analysis indicates that hostile feelings toward LGBT rights are particularly widespread among boys, while the effects of socioeconomic status and parental education remain limited. Various religious denominations proved to have a strong and significant negative impact on tolerance, with especially high scores for Islam. Religious practice, too, contributes to a negative attitude toward LGBT rights. The consequences of these findings with regard to tolerance for gay rights among Islamic youth in Western democracies are discussed.