Vision and visual cortical maps in mice with a photoreceptor synaptopathy: reduced but robust visual capabilities in the absence of synaptic ribbons.

How little neurotransmission in the visual system is sufficient to promote decent visual capabilities? This question is of key importance for therapeutic approaches to restore vision in patients who suffer from degenerative retinal diseases. In the retinae of mice, mutant for the presynaptic scaffolding protein Bassoon (Bsn), signal transfer at photoreceptor ribbon synapses is severely disturbed due to impaired ribbon attachment to the active zone. We have used two different behavioural tasks and optical imaging of intrinsic signals to probe vision in young and adult Bsn-/- mice and their wild-type littermates. Here we show that while visual acuity was significantly reduced in mutants compared to controls, vision guided behavioural decisions and optical imaging revealed essentially unperturbed cortical signals and retinotopy in spite of the photoreceptor synaptopathy. In addition, both vision and visual cortical maps were adult-like at 4 weeks of age. These results show that (i) while Bassoon-dependent fast exocytosis is essential for normal vision surprisingly good visual performance can be achieved in the absence of synaptic ribbons, (ii) both the development and maintenance of visual cortical maps is independent of synaptic ribbons and (iii) visual development in the mutants is completed at 4 weeks of age indicating that later developing ectopic synapses do not affect vision. Thus, the central visual system can make use of slow and weak retinal signals to subserve surprisingly robust vision.

The presynaptic active zone protein bassoon is essential for photoreceptor ribbon synapse formation in the retina.

The photoreceptor ribbon synapse is a highly specialized glutamatergic synapse designed for the continuous flow of synaptic vesicles to the neurotransmitter release site. The molecular mechanisms underlying ribbon synapse formation are poorly understood. We have investigated the role of the presynaptic cytomatrix protein Bassoon, a major component of the photoreceptor ribbon, in a mouse retina deficient of functional Bassoon protein. Photoreceptor ribbons lacking Bassoon are not anchored to the presynaptic active zones. This results in an impaired photoreceptor synaptic transmission, an abnormal dendritic branching of neurons postsynaptic to photoreceptors, and the formation of ectopic synapses. These findings suggest a critical role of Bassoon in the formation and the function of photoreceptor ribbon synapses of the mammalian retina.

Structural and functional remodeling in the retina of a mouse with a photoreceptor synaptopathy: plasticity in the rod and degeneration in the cone system.

Knowledge about the plastic and regenerative capacity of the retina is of key importance for therapeutic approaches to restore vision in patients who suffer from degenerative retinal diseases. In the retinae of mice, mutant for the presynaptic scaffolding protein Bassoon, signal transfer at photoreceptor ribbon synapses is disturbed due to impaired ribbon attachment to the active zone. In a long-term study we observed, with light and electron microscopic immunocytochemistry and electroretinographic recordings, two overlapping events in the Bassoon mutant retina, i.e. loss of photoreceptor synapses in the outer plexiform layer, and structural remodeling and formation of ectopic photoreceptor synapses in the outer nuclear layer, a region usually devoid of synapses. Formation of ectopic synaptic sites starts around the time when photoreceptor synaptogenesis is completed in wild-type mice and progresses throughout life. The result is a dense plexus of ectopic photoreceptor synapses with significantly altered but considerable synaptic transmission. Ectopic synapse formation is led by the sprouting of horizontal cells followed by the extension of rod bipolar cell neurites that fasciculate with and grow along the horizontal cell processes. Although only the rod photoreceptors and their postsynaptic partners show structural and functional remodeling, our study demonstrates the potential of the retina for long-lasting plastic changes.