Controlling the Gain of Rod-Mediated Signals in the Mammalian Retina

Abstract

Effective sensory processing requires matching the gain of neural responses to the range of signals encountered. For rod vision, gain controls operate at light levels at which photons arrive rarely at individual rods, light levels too low to cause adaptation in rod phototransduction. Under these conditions, adaptation within a conserved pathway in mammalian retina maintains sensitivity as light levels change. To relate retinal signals to behavioral work on detection at low light levels, we measured how background light affects the gain and noise of primate ganglion cells. To determine where and how gain is controlled, we tracked rod-mediated signals across the mouse retina. These experiments led to three main conclusions: (1) the primary site of adaptation at low light levels is the synapse between rod bipolar and AII amacrine cells; (2) cellular noise after the gain control is nearly independent of background intensity; and (3) at low backgrounds, noise in the circuitry, rather than rod noise or fluctuations in arriving photons, limits ganglion cell sensitivity. This work provides physiological insights into the rich history of experiments characterizing how rod vision avoids saturation as light levels increase.

Calcium spike-mediated digital signaling increases glutamate output at the visual threshold of retinal bipolar cells

“…Instead, Mbs synapse directly onto GCs (Marc and Liu 2000;Palmer 2010;Witkovsky and Dowling 1969). Interestingly, the scotopic threshold, or, in other words, the minimal stimulus intensity that activated dark-adapted mouse RBCs, was found to be ϳ0.03 rhodopsin photoisomerization (Rh*)/rod (Dunn et al 2006;Saszik et al 2002). This stimulus intensity is the equivalent of 0.07 photons· m Ϫ2 ·s Ϫ1 presented for 500 ms (Pang et al 2004) and is similar to the scotopic threshold of Mb signaling (Fig.…”

“…The mammalian retina utilizes a dedicated circuitry for processing light signals around the absolute visual threshold, the rod¡RBC¡AII amacrine¡cone BC¡GC pathway (Bloomfield and Dacheux 2001), which allows for gain control/amplification at multiple stages (Schwartz and Rieke 2013). AII amacrine cells amplify RBC output, set the visual threshold for GCs, and also provide a gain control mechanism to ensure luminance encoding over a wide range of light intensities (Arman and Sampath 2012;Dunn et al 2006). However, the fish retina does not have an AIIequivalent cell that collects outputs of dozens of Mbs and amplifies the signal before forwarding it toward GCs.…”

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision

“…Different adaptational mechanisms set in at different time points following stimulation. Examples for rather slow mechanisms are changes in the signal amplification of the phototransduction cascade and certain changes in the gain of synaptic transmission 33,34 . In contrast, HCN1 channel feedback provides a rapid adaptational mechanism that affects rod photoreceptor signals just past the leading edge.…”

Electrical synapses between AII amacrine cells in the retina: Function and modulation

“…Second, Dunn et al (2006) found that there was an approximately twofold increase in noise in the absence of electrical coupling when they compared visual responses of AII amacrines in wild-type and Cx36 KO mice. Hampson et al (1992) suggested that the effects of dopamine and dopaminergic agonists and antagonists on the extent of tracer coupling of AII amacrines were mediated by changes in the phosphorylation of the connexin(s) involved and that the reduction of coupling was mediated by D1-type dopamine receptors and activation of the cAMP -PKA pathway.…”