A Positive Feedback Synapse from Retinal Horizontal Cells to Cone Photoreceptors

Skyler L Jackman,Wallace B Thoreson,Norbert Babai,Richard H Kramer,James J Chambers,Fred Rieke

doi:10.1371/journal.pbio.1001057

Abstract

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca2+ and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca2+, whereas negative feedback is mediated by a change in HC membrane potential. Local uncaging of AMPA receptor agonists suggests that positive feedback is spatially constrained to active HC-cone synapses, whereas the negative feedback signal spreads through HCs to affect release from surrounding cones. By locally offsetting the effects of negative feedback, positive feedback may amplify photoreceptor synaptic release without sacrificing HC-mediated contrast enhancement.

Highlights

The retina is an exceptionally approachable part of the brain, deciphering the retinal neural circuit was one of the earliest triumphs of systems neuroscience [1]
The positive feedback signal is constrained to individual horizontal cell– photoreceptor connections, whereas the negative feedback signal spreads throughout a horizontal cell to affect many surrounding photoreceptors
We found that AMPA increased vesicular release from retinal photoreceptors in species across several phyla, including zebrafish (Danio rerio), tiger salamander (Ambystoma tigrinum), anole lizard (Anolis carolinensis), and rabbit (Oryctolagus cuniculus) (Figure S1)

Summary

Introduction

The retina is an exceptionally approachable part of the brain, deciphering the retinal neural circuit was one of the earliest triumphs of systems neuroscience [1]. Voltage changes in HCs result in sign-inverted voltage changes in cone photoreceptors, a negative feedback connection. HCs project laterally in the retina over hundreds of microns and integrate inputs from many rods and cones, so negative feedback causes cones [3] and rods [5] to have an antagonistic center-surround receptive field. This receptive field organization is reflected postsynaptically first in bipolar cells [2] and in subsequent neuronal layers of the visual system [6], enhancing the neural representation of spatial contrast and sharpening visual detection of edges

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Discussion

Conclusion