Crossover inhibition provides a variety of enhancements and corrections to the nonlinear rectified visual signals that course through the retina. This section summarizes six different ways in which crossover inhibition corrects for nonlinearities and enhances visual function.
Crossover inhibition converts Y-like responses into X-like responses to an inverting grating
Generation of Y-like nonlinear responses
Nonlinear rectifying cat Y cells respond with a transient burst of spikes to each grating inversion (Levick, 1965
; Enroth-Cugell & Robson, 1984
; Demb et al., 1999
). This nonlinear characteristic was identified as rectification (Richter & Ullman, 1982
; Enroth-Cugell & Robson, 1984
). Ganglion cells that respond to inverting gratings (Hamasaki & Sutija, 1979
; Hamasaki et al., 1979
; Demb et al., 2001
) have been shown to receive nonlinear rectifying excitatory input from bipolar cells similar to the signals shown in (Roska & Werblin, 2001
; Roska et al., 2006
). In recent studies of the crossover nonlinearity measuring synaptic currents
, evidence of rectification is given by the asymmetric synaptic currents measured in ganglion cells at the onset and termination of the flash as shown in . The left panel in shows how the nonlinear rectified responses measured intracellularly as asymmetrical currents in ganglion cells could lead to nonlinear spike activity, namely a burst of spikes each time the grating inverts. When the grating inverts, the increase in excitatory currents at the bright stripes is larger than the decrease in excitation at the dark stripes (). Synaptic input to the ganglion cell from the bright-going and the dark-going stripe regions add (), so every inversion of the grating elicits net transient excitation and concomitant spiking (). This response is similar to that found earlier in Y-type cat ganglion cells (Enroth-Cugell & Robson, 1984
Fig. 5 Superposition of the excitatory and inhibitory currents in a population of ON ganglion cells leading to null response to inverting grating. Left column: nonlinear responses without crossover. Right column: responses linearized by crossover. The initiation (more ...) Generation of X-like linear responses
One of the criteria for linearity in the earlier studies was the null response to luminance-neutral inverting gratings. This is characteristic of cat X cells (Enroth-Cugell & Robson, 1966
; Richter & Ullman, 1982
; Enroth-Cugell & Freeman, 1987
). Despite the local changes in luminance, the overall luminance of an inverting grating remains constant. This condition comes about through two separate current additions as illustrated in the following: The excitatory synaptic inputs from two ON bipolar cells, one beneath the bright-going stripe and the other beneath the dark-going stripe, are shown by the pair of excitatory responses in . These two excitatory currents would generate a net excitation with each inversion of the grating as shown in . But with crossover (), the rectified excitatory current in each stripe () is added to an inhibitory current as shown in . The two currents under each stripe are now symmetrical () but equal and opposite. When these two currents are added at the ganglion cell membrane (), two currents oppose each other, so the postsynaptic voltage response of the cell is not modulated () and spiking does not occur ().
Crossover inhibition converts a passive antagonistic surround at the outer retina into an active antagonistic surround at the inner retina
shows the spatial profile of activity across a population of ON bipolar cells across and outside the region of a flashed light bar. In the region coincident with the bar, the ON bipolar cells are depolarized, and in the regions adjacent to the bar, the bipolar cells are hyperpolarized due to the action of horizontal cells that project their antagonistic activity laterally from the region of the bar (). ON ganglion cells receive a rectified input from these ON bipolar cells: the ganglion cells receive an inward current in regions beneath the bar, but in regions adjacent to the bar, there is little outward current because rectification has truncated release there (). The OFF bipolar cells respond to the dark bar in a complementary way: they decrease release in regions beneath the bar but act to depolarize amacrine cells in regions adjacent to the bar. These amacrine cells in adjacent regions actively inhibit ganglion cells adjacent to the bar as shown in . The excitatory and inhibitory currents add to generate a response profile for the ON ganglion cells () that resembles the profile of the ON bipolar cell A more closely than either the excitatory or the inhibitory currents arriving at the ganglion cells B and C. Moreover, what was only a decrease in activity in the surround measured in the bipolar cell is transformed into an active inhibition at the ganglion cell level. In this way, crossover provides an additional active current, increasing the antagonistic effect from the surround.
Fig. 6 Crossover creates an active antagonistic surround. (A) Original spatial profile of voltage responses for a population of ON bipolar cells in response to a bright stripe. The width of the stripe is shown in the dotted trace. (B) Voltage profile for an (more ...)
Crossover inhibition extends the range of intensities to the scotopic level for cone-driven ganglion cells
Earlier studies (Pang et al., 2003
; Manookin et al., 2008
) showed that crossover signals, mediated by AII amacrine cells, add to the synaptic input to extend the sensitivity range of OFF alpha cells. In those studies, it appears that the more sensitive rod signals are conveyed synaptically to the OFF bipolar cells via
the AII amacrine cells as shown in . There is also the possibility of similar crossover signals in salamander (Pang et al., 2007
Fig. 7 Crossover enhances low light sensitivity via AII amacrine cells. OFF bipolar cells provide excitation to the OFF ganglion cell. Rod bipolar cells excite AII amacrine cells via a conventional glutamate synapse. AII amacrine cells convey crossover ON inhibition (more ...)
Crossover inhibition reduces the net change in input conductance
It is evident from and that excitation and inhibition generate opposing conductance changes. Each increase in conductance from the excitatory input is offset by a decrease in conductance from the inhibitory input as summarized in . The combination of these two opposing conductance inputs tends to reduce the net conductance change in the postsynaptic neuron. This is valuable because other inputs to the neuron will not be modified at different states of excitation or inhibition.
Fig. 8 Crossover inhibition reduces conductance changes in the postsynaptic neuron. Traces extracted from . In the ON cell at light ON, the inward excitatory current is associated with a conductance increase, but the inward inhibitory current is associated (more ...)
As a consequence of these opposing conductance changes, the I–V curve for the total light-elicited conductance will tend to become less steep. If the conductance changes were exactly equal and opposite, there would be no net conductance and the I–V curve would be horizontal, never crossing the voltage axis.
Crossover inhibition can eliminate signal offsets that are common to all neurons
illustrates how crossover inhibition could compensate for membrane potential offsets that would be common to both excitation and inhibition in the retina. Such offsets could come about because of changes in extracellular potassium concentration or changes in other factors that would offset membrane potential in all neurons. In this example, the input is a sinusoidally modulated illumination. At the midpoint of the traces, all neurons have been subjected to a common depolarization. In the left column, the membrane voltages of the bipolar cell and the amacrine cell become more positive. In the middle column, excitation from the bipolar cell and inhibition from the amacrine cell bring both sinusoidal inputs in phase, but membrane potential current offsets cancel. This leads to a sinusoidal output that is in phase with the original excitatory input but with no sign of the offset. This function is valuable because it decreases distortions to the visual signal due to perturbations within the retina.
Fig. 9 Crossover corrects for offsets in retinal circuitry. At the midpoint of the traces the voltages of the OFF bipolar and ON amacrine cells become more positive. At the ganglion cell, the bipolar cell current becomes more inward, but the inhibitory current (more ...)
Crossover inhibition allows the retina to distinguish luminance from contrast
The rectifying nonlinearity can lead to confusion between luminance and contrast. replicates a measurement that illustrates this point. The signal in is a voltage trace in a retinal neuron where the retina has been stimulated by a sinusoid that is amplitude modulated by a slower sinusoid. One can consider the faster sinusoid as a contrast signal around a steady luminance represented by the average value of the signal. The postsynaptic excitation shown in , generated by this neuron, shows an offset of the luminance value caused by synaptic rectification. The postsynaptic inhibition shown in also shows the offset but in the opposite direction. When excitation and inhibition are combined, the final output voltage resembles more closely the input signal with little luminance offset shown in . This is valuable for maintaining the difference between contrast and luminance.
Fig. 10 Crossover inhibition eliminates confusion between contrast and luminance. (A) Fast sinusoidal illumination modulated by a slower frequency sinusoid. (B and C) Rectified currents in postsynaptic ganglion cell. In this case, rectification causes an artifactual (more ...)