Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 May 29;39(22):4312-4322.
doi: 10.1523/JNEUROSCI.3066-18.2019. Epub 2019 Mar 29.

Simulated Saccadic Stimuli Suppress ON-Type Direction-Selective Retinal Ganglion Cells via Glycinergic Inhibition

Benjamin Sivyer  1 , Alexander Tomlinson  1 , W Rowland Taylor  2
Affiliations

Simulated Saccadic Stimuli Suppress ON-Type Direction-Selective Retinal Ganglion Cells via Glycinergic Inhibition

Benjamin Sivyer et al. J Neurosci. .

Abstract

Two types of mammalian direction-selective ganglion cells (DSGCs), ON and ONOFF, operate over different speed ranges. The directional axes of the ON-DSGCs are thought to align with the axes of the vestibular system and provide sensitivity at rotational velocities that are too slow to activate the semicircular canals. ONOFF-DSGCs respond to faster image velocities. Using natural images that simulate the natural visual inputs to freely moving animals, we show that simulated visual saccades suppress responses in ON-DSGCs but not ONOFF-DSGCs recorded in retinas of domestic rabbits of either gender. Analysis of the synaptic inputs shows that this saccadic suppression results from glycinergic inputs that are specific to ON-DSGCs and are absent in ONOFF-DSGCs. When this glycinergic input is blocked, both cell types respond similarly to visual saccades and display essentially identical speed tuning. The results demonstrate that glycinergic circuits within the retina can produce saccadic suppression of retinal ganglion cell activity. The cell-type-specific targeting of the glycinergic circuits further supports the proposed physiological roles of ON-DSGCs in retinal-image stabilization and of ONOFF-DSGCs in detecting local object motion and signaling optical flow.SIGNIFICANCE STATEMENT In the mammalian retina, ON direction-selective ganglion cells (DSGCs) respond preferentially to slow image motion, whereas ONOFF-DSGCs respond better to rapid motion. The mechanisms producing this different speed tuning remain unclear. Here we show that simulated visual saccades suppress ON-DSGCs, but not ONOFF-DSGCs. This selective saccadic suppression is because of the selective targeting of glycinergic inhibitory synaptic inputs to ON-DSGCs. The different saccadic suppression in the two cell types points to different physiological roles, consistent with their projections to distinct areas within the brain. ON-DSGCs may be critical for providing the visual feedback signals that contribute to stabilizing the image on the retina, whereas ONOFF-DSGCs may be important for detecting the onset of saccades or for signaling optical flow.

Keywords: electrophysiology; neural circuits; retina; visual processing.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Simulated saccades suppress preferred-direction responses in ON but not ONOFF-DSGCs. A, Images used for simulated saccades. Left, An example checkerboard. Right, the natural scene used. The image sizes were extended outside the projection area to allow for generation of saccades. The red rectangles show the size of the stimulus DLP array, and the blue circles show the area projected onto the retina. The yellow circles show the approximate extent of a typical ON-DSGC dendritic arbor. See Materials and Methods for details on intensities and dimensions. B, Average PSTHs from ONOFF- (red, n = 7) and ON- (black, n = 10) DSGCs during stimulation with the drifting checkerboard shown in A. Shading shows the SEM. The symbols show the timing and direction of saccades (blue, preferred; green, null). C, Average PSTHs for ONOFF- (red; n = 10) and ON- (black; n = 8) DSGCs during stimulation with the drifting natural image shown in A. Raster plots for several ON-DSGCs during the natural scene stimulation are shown. Each line of dots shows the timing of the spikes during a single trial. Different cells are shown alternately in gray and black. The trace at the bottom of the figure shows the position of the stimuli along the preferred-null axis as a function of time, i.e., the slope represents the speed. Speed of saccades was 90°/s. In the intervals between saccades the positive slope indicates the constant drift of the image in the preferred direction (0.6°/s). The same stimulus trajectory was used for natural scenes and checkerboards. The vertical broken lines mark the saccade onsets, with blue and green lines marking the preferred- and null-direction events, respectively.
Figure 2.
Figure 2.
The decrease in directional responses in ONOFF-DSGCs during rapid global motion only occurs at very high stimulus speeds. Averaged spike responses (8 cells) to simulated rapid eye movements in the preferred and null directions at image velocities producing clear directional responses of ONOFF-DSGCs (10°/s). The checkerboard stimulus and the times at which the rapid motion events occurred was the same as in Figure 1. In one set of trials, stimuli moved only in the preferred direction (blue) and in a second set, stimuli moved in the preferred and null directions (black).
Figure 3.
Figure 3.
Speed tuning of ON- (black) and ONOFF- (red) DSGCs. A, Average PSTHs recorded for a moving full-field checkerboard stimulus. The stimulus appeared and after a 1 s delay began drifting in the preferred direction at 0.6°/s for 4 s before abruptly increasing speed. This stimulus timing is shown beneath the traces. ON-DSGCs shown in black (n = 3) and ONOFF-DSGCs in red (n = 4). B, Average PSTHs recorded for ON- (black; n = 11) and ONOFF- (red; n = 12) DSGCs in response to a bright bar on a gray background drifted across the receptive field center in the preferred direction at the speeds indicated. The length of the bar was adjusted to separate leading and trailing edge responses. Inset; replot of the PSTHs for the ON-DSGCs with the time axis rescaled so that the responses to the leading and trailing edges of the stimulus were superimposed. The calibration bars beneath the traces all denote 4 s, according to the speed and length of the stimulus bars. C, Speed-dependence of spike responses to global (filled symbols) and local motion (open symbols) for ON-DSGCs (black) and ONOFF-DSGCs (red; on response only). Data drawn from cells in A and B. D, Expanded segment of the PSTHs from A normalized in time to show the correspondence of the responses to the spatial structure of the stimuli.
Figure 4.
Figure 4.
ON-DSGCs but not ONOFF-DSGCs receive a transient inhibitory input that is activated at high flicker frequencies. Responses to a flickering spot centered on the receptive field to illustrate the temporal tuning. A, Simultaneous voltage recordings from adjacent ON- and ONOFF-DSGCs with overlapping receptive fields at a range of temporal frequencies. Stimulus timing is shown by the overlying the traces. B, Average voltage responses from 10 ON-DSGCs during 1, 2, 4, and 8.5 Hz sinusoidal flicker stimulation. Shading shows the SD; stimulus timing is superimposed in gray. C, Phase of the peak IPSP versus stimulus frequency measured from the second stimulus cycle. The solid line shows the linear regression. The slope of the line corresponds to a fixed time delay of 19.3 ms.
Figure 5.
Figure 5.
A rapid transient inhibitory synaptic conductance is observed ON-DSGCs. A1, The stimulus was a sinusoidally-modulated 300 μm diameter spot, 80% contrast centered on the receptive field. A2, A3, Net light-evoked inhibitory and excitatory synaptic conductances activated by a range of flicker frequencies (for details of analysis, see Materials and Methods). Within each trial the spot was flickered at three frequencies, as indicated by the stimulus timing beneath each trace. Shading shows the SEM (top, n = 9 cells; bottom, n = 6 cells). The arrows highlight the inhibition activated during the OFF-phase of the stimulus. The symbols above the 2 Hz responses illustrate the measurement points for B. The triangles represent the peak amplitude during the first half stimulus cycle, and the circles show the amplitude during the second cycle. B, Peak amplitude of the inhibitory and excitatory conductances at the stimulus-cycle time-points indicated in A2 and A3.
Figure 6.
Figure 6.
Inhibitory synaptic inputs to ON-DSGCs comprise direct glycinergic inputs. A, Average inhibitory and excitatory conductances recorded in control (black) and during application of 10 μm SR95531 + 10 μm TPMPA (GABA block, green; n = 5). Top row shows inhibition; bottom row shows excitation. Sinusoidal flicker frequency indicated beneath. Three recordings remained stable enough for the subsequent addition of 1 μm strychnine (GABA + Glycine block, magenta; n = 3). Centered light spot, 300 μm diameter, 80% contrast. B, Average inhibitory and excitatory conductances generated by a bar (300 μm wide, 5000 μm long, 1600 μm/s, 80% contrast) moving through the center of the receptive field in the preferred motion. Traces show control (black), GABAergic block (green; n = 5), and subsequent GABAergic and glycinergic block (magenta; n = 4, TPMPA 10 μm, SR95531 10 μm, strychnine 1 μm). The grey lines show the control traces scaled to match the maximum amplitude during drug application to compare the time course of the excitation during inhibitory block.
Figure 7.
Figure 7.
Speed-tuning in ON- and ONOFF-DSGCs is similar after glycinergic block. A, Representative voltage responses during center flicker (diameter, 300 μm; contrast, 80%) at two frequencies as indicated in control (black; replotted from Fig. 4A) and in the presence of 1 μm strychnine (blue). B, Average synaptic conductances (n = 4) activated by a centered stimulus spot (diameter, 300 μm; contrast, 80%) modulated at 8.5 Hz, in control (black) and in the presence of 1 μm strychnine (blue). C, PSTHs in response to global drift of a random checkerboard stimulus similar to that shown in Figure 1. Average of six ON-DSGCs in control and during glycinergic block. The arrows highlight preferred and null direction saccades. Spiking increases in both cases. D, PSTHs averaged from four ONOFF-DSGCs and seven ON-DSGCs before (black) and during application of strychnine (blue). Shading shows SEM. Light stimulus was a 300 μm wide bar (same stimulus as Fig. 3B) drifting in the preferred direction at various velocities. Speed of the stimulus indicated next to the traces. E, Peak spike rates shown for the full range of stimulus velocities. Circles show the ON-response of the ONOFF-DSGCs. The scaling of the y-axes is set to normalize the amplitude.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ackert JM, Farajian R, Völgyi B, Bloomfield SA (2009) GABA blockade unmasks an OFF response in ON direction selective ganglion cells in the mammalian retina. J Physiol 587:4481–4495. 10.1113/jphysiol.2009.173344 - DOI - PMC - PubMed
    1. Amthor FR, Keyser KT, Dmitrieva NA (2002) Effects of the destruction of starburst-cholinergic amacrine cells by the toxin AF64A on rabbit retinal directional selectivity. Vis Neurosci 19:495–509. 10.1017/S0952523802194119 - DOI - PubMed
    1. Angelaki DE, Cullen KE (2008) Vestibular system: the many facets of a multimodal sense. Annu Rev Neurosci 31:125–150. 10.1146/annurev.neuro.31.060407.125555 - DOI - PubMed
    1. Ariel M, Daw NW (1982) Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells. J Physiol 324:161–185. 10.1113/jphysiol.1982.sp014105 - DOI - PMC - PubMed
    1. Barlow HB, Hill RM (1963) Selective sensitivity to direction of movement in ganglion cells of the rabbit retina. Science 139:412–414. 10.1126/science.139.3553.412 - DOI - PubMed

Publication types

LinkOut - more resources