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Ribbon synapses mediate continuous release in neurons that have graded voltage responses. While mammalian retinas can signal visual flicker at 80-100 Hz, the time constant, τ, for the refilling of a depleted vesicle release pool at cone photoreceptor ribbons is 0.7-1.1 s. Due to this prolonged depression, the mechanism for encoding high temporal frequencies is unclear. To determine the mechanism of high-frequency signaling, we focused on an "Off" cone bipolar cell type in the ground squirrel, the cb2, whose transient postsynaptic responses recovered following presynaptic depletion with a τ of ∼0.1 s, or 7- to 10-fold faster than the τ for presynaptic pool refilling. The difference in recovery time course is caused by AMPA receptor saturation, where partial refilling of the presynaptic pool is sufficient for a full postsynaptic response. By limiting the dynamic range of the synapse, receptor saturation counteracts ribbon depression to produce rapid recovery and facilitate high-frequency signaling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Decades of research have focused on the circuit connectivity between retinal neurons, but only a handful of amacrine cells have been described functionally and placed in the context of a specific retinal circuit. Here, we identify a circuit where inhibition from a specific amacrine cell plays a vital role in shaping the feature selectivity of a postsynaptic ganglion cell. We record from transgenically labeled CRH-1 amacrine cells and identify a postsynaptic target for CRH-1 amacrine cell inhibition in an atypical retinal ganglion cell (RGC) in mouse retina, the Suppressed-by-Contrast (SbC) RGC. Unlike other RGC types, SbC RGCs spike tonically in steady illumination and are suppressed by both increases and decreases in illumination. Inhibition from GABAergic CRH-1 amacrine cells shapes this unique contrast response profile to positive contrast. We show the existence and impact of this circuit, with both paired recordings and cell-type-specific ablation., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

A cone photoreceptor releases glutamate at ribbons located atop narrow membrane invaginations that empty onto a terminal base. The unique shape of the cone terminal suggests that there are two transmitter microenvironments: within invaginations, where concentrations are high and exposures are brief; and at the base, where concentrations are low and exposure is smoothed by diffusion. Using multicell voltage-clamp recording, we show that different subtypes of Off bipolar cells sample transmitter in two microenvironments. The dendrites of an AMPA receptor-containing cell insert into invaginations and sense rapid fluctuations in glutamate concentration that can lead to transient responses. The dendrites of kainate receptor-containing cells make basal contacts and respond to a smoothed flow of glutamate that produces sustained responses. Signaling at the cone to Off bipolar cell synapse illustrates how transmitter spillover and synapse architecture can combine to produce distinct signals in postsynaptic neurons.

Background: Cone photoreceptors are noisy because of random fluctuations of photon absorption, signaling molecules, and ion channels. However, each cone's noise is independent of the others, whereas their signals are partially shared. Therefore, electrically coupling the synaptic terminals prior to forward transmission and subsequent nonlinear processing can appreciably reduce noise relative to the signal. This signal-processing strategy has been demonstrated in lower vertebrates with rather coarse vision, but its occurrence in mammals with fine acuity has been doubted (even though gap junctions are present) because coupling would blur the neural image., Results: In ground squirrel retina, whose triangular cone lattice resembles the human fovea, paired electrical recordings from adjacent cones demonstrated electrical coupling with an average conductance of approximately 320 pS. Blur caused by this degree of coupling had a space constant of approximately 0.5 cone diameters. Psychophysical measurements employing laser interferometry to bypass the eye's optics suggest that human foveal cones experience a similar degree of neural blur and that it is invariant with light intensity. This neural blur is narrower than the eye's optical blur, and we calculate that it should improve the signal-to-noise ratio at the cone terminal by about 77%., Conclusions: We conclude that the gap junctions observed between mammalian cones, including those in the human fovea, represent genuine electrical coupling. Because the space constant of the resulting neural blur is less than that of the optical blur, the signal-to-noise ratio can be markedly improved before the nonlinear stages with little compromise to visual acuity.

A proton pump acidifies synaptic vesicles and provides the electrochemical gradient for transmitter uptake. Although external protons can modulate membrane voltage- and ligand-gated conductances, the fate of the protons released when vesicles fuse with the plasma membrane is unclear. In the dark, the glutamate-laden vesicles of cone photoreceptors fuse continuously with the plasma membrane. I now show that vesicular protons feed back to block the nearby calcium channels that mediate release. This local proton-mediated feedback is a novel mechanism through which neurons may regulate the release of transmitter.

Unlike cone photoreceptors, whose light responses have a uniform time course, retinal ganglion cells are tuned to respond to different temporal components in a changing visual scene. The signals in a mammalian cone flow to three to five morphologically distinct "OFF" bipolar cells at a sign-conserving, glutamatergic synapse. By recording simultaneously from pairs of synaptically connected cones and OFF bipolar cells, I now show that each morphological type of OFF bipolar cell receives its signal through a different AMPA or kainate receptor. The characteristic rate at which each receptor recovers from desensitization divides the cone signal into temporal components. Temporal processing begins at the first synapse in the visual system.