The ON Pathway Rectifies the OFF Pathway of the Mammalian Retina

Abstract

In the vertebrate visual system, ON cells respond to positive contrasts and OFF cells respond to negative contrasts, and thus both ON and OFF cells exhibit rectification. We investigated the retinal circuits by which the ON pathway rectifies the OFF pathway. White noise was projected onto an in vitro preparation of the mammalian retina and excitatory currents were recorded from retinal ganglion cells under whole-cell voltage clamp. Currents in OFF cells were more rectified than those in ON cells: thus, currents in ON cells were able to signal both positive and negative contrasts, but currents in OFF cells were virtually restricted to negative contrasts. Blocking signals in the ON pathway derectified currents in OFF ganglion cells, thus allowing them to be modulated by positive contrasts, indicating that the ON pathway normally rectifies currents in OFF ganglion cells. Such cross-rectification from ON to OFF pathways required intact glycinergic inhibition, indicating that a glycinergic amacrine cell, most likely the AII amacrine cell, allows the ON bipolar cell to hyperpolarize the OFF bipolar cell close to the threshold for transmitter release, thus rectifying excitatory currents in the OFF ganglion cell. Asymmetrical rectification of ON and OFF cells may be an adaptation to natural scenes that have more contrast levels below the mean than above. Thus, in order for ON and OFF pathways to encode an equal number of contrast levels, the ON cells must signal some negative contrasts.

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

“…However, we cannot exclude amacrine cell pathways that may contribute to the ganglion cell surround (Fried et al 2006). Neurons in the OFF pathway cannot be isolated pharmacologically and also receive cross-inhibition from the ON pathway (Liang and Freed 2010), making it harder to disentangle their relative contributions to OFF ganglion cell spikes. The presented model (Figs.…”

Some Principles of Retinal Design: The Proctor Lecture

“…23 The rectification (separate pathways for negative and positive contrasts) is incomplete because the ON pathways retain, via clever circuits, some capacity to encode negative contrasts. 24,25 Moreover, these circuits allow the ON pathway to increase coding efficiency in the OFF pathway (Liang Z and MA Freed, unpublished observations, 2012). These circuit features serve the general principle: apportion more neural resources to encode the richer sources of information.…”

Glycine receptor alpha subunit (GlyRa) specific inhibition contributes to ganglion cell signaling in mouse retina.

“…In the retina, glycinergic inhibition has been primarily associated with an On-to-Off crossover pathway, which appears to: enhance excitatory/inhibitory responses of OFF RGCs to luminance decrement/increment (Buldyrev et al, 2012;Demb and Singer, 2012;Liang and Freed, 2010;Manookin et al, 2008;Murphy and Rieke, 2006;Roska et al, 2006), regulate contrast gain control , contribute to the linearity of the retinal output (Molnar et al, 2009) and shape RGCs responses to specific visual stimuli (Cafaro and Rieke, 2013;Münch et al, 2009). …”

“…Furthermore, crossover inhibition is hypothesized to modify an inherently nonlinear synaptic current making it more linear to extend the operating range of RGC coding (Molnar et al, 2009). Many studies have shown modulation from On pathways to OFF BCs and RGCs and AII cell is a candidate that mediates crossover interaction (Chen et al, 2010;Liang and Freed, 2010;Manookin et al, 2008;Rieke, 2006, 2008;van Wyk et al, 2009). Although less studied, Off to On crossover pathway inhibition is also observed in the inner retina (Molnar et al, 2009).…”