Information encoding at the first synapse in vision

Animal visual systems are adapted to extract and process behaviourally important information from the environment. How visual information is encoded at the first synapse in the retina determines the quality of information available downstream. Accordingly, investing into a highly reliable photoreceptor synapse is critical. But how reliable is reliable?

Working on larval zebrafish as a model, here it is shown that ancestral red-cones (LWS1) encode luminance information in vivo with extreme accuracy and reliability. LWS1 cones are conserved in nearly all vertebrate lineages, including in mammals. They are generally thought to underpin the bulk of diurnal greyscale processing, alongside species-specific roles in spectral processing. I used in vivo two-photon imaging to establish how single red-cones encode steps of light at the level of glutamate release. To this end, SFiGluSnFR was expressed in the post-synaptic horizontal cells, which allowed us to use their dendritic processes as cone-specific “glutamate-antennae”.

It was found that red-cones encode and transmit off-steps of light in an exceptionally reliable and temporally precise manner, contrasting strongly to Poisson-distributed release observed at central synapses in the brain. Red-cones exhibit a rapid recovery of the readily releasable pool of vesicles, which likely underpins reliability in signal transmission. Stimulating the retina with positive and negative steps of light demonstrated that red-cones encode contrast in a balanced fashion, through bi-directional modulation of glutamate release. Together, the results describe a highly precise and reliable first synapse in the visual system, capable of encoding both positive and negative contrasts.

How does local circuitry contribute to red-cone signalling?Horizontal cell (HC) feedback was pharmacologically blocked to understand how outer retinal circuits shape contrast-encoding and the high reliability of red-cone signal transmission. Red-cones in isolation tend to lose their responses to positive contrasts, and the contrast-response function becomes less linear. Moreover, glutamate release events are delayed. Taken together, the data provides the first in vivo evidence for a positive feedback mechanism from HCs to red-cones, which increases baseline glutamate release to linearise the output of red-cones in response to contrast, and accelerates glutamate release.

Together, the data demonstrate that red-cones are a reliable and temporally precise channel for the detection of changes in luminance, with HC feedback determining the linearity of the output underpinning much of the zebrafish’s achromatic vision.