Abstract
Abstract: :
Purpose:In a mutant mouse retina lacking a functional Bassoon protein, the photoreceptor ribbons are not anchored to the presynaptic membrane and photoreceptor synaptic transmission is greatly impaired (Dick et al., 2003, Neuron 37: 775–786). We studied the long time effects of the lack of Bassoon on the structure and function of the retina. Methods: With immunocytochemistry and confocal laser–scanning microscopy, we examined the neurons and synapses in wild–type and mutant retinae from postnatal week 1 up to 1–2 years postnatally. In a functional analysis, ERG recordings of wild–type and mutant retinae were performed at different postnatal stages. Results: Up to 2 weeks postnatally, wild–type and mutant retinae are indisdinguishable by their structure. Between postnatal week 2 and 3 first few horizontal cell processes and bipolar cell dendrites in the mutant retina arborize in the outer nuclear layer. Here they contact ectopic synaptic sites which appear around the same time. Ectopic synapses are formed only by rods and not by cones. With increasing age, the number of ectopic synaptic sites, the number of sprouting processes and their branching density gradually increases. The structural and synaptic alterations in the outer retina of the mutant mouse are reflected in the ERG recordings. Mutant mice younger than 1 month show little to no b–wave and are practically blind. In older mutant mice it was possible to record a scotopic ERG. The b–wave, however, developed significantly slower, lasted longer and its amplitude was significantly smaller compared to wild–type littermates. Conclusions: Loss of Bassoon prevents normal photoreceptor synaptic development and signaling. Strikingly, the mutant retina shows a yet unknown reactive plasticity with the genesis of ectopic photoreceptor synapses and the partial restoration of photoreceptor synaptic transmission. Only the rod system but not the cone system has this regenerative power.
Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • transgenics/knock–outs • protein structure/function