Yuko Sugita

Contributions of retinal direction‐selective ganglion cells to optokinetic responses in mice

In the mouse retina, there are two distinct groups of direction‐selective ganglion cells, ON and ON–OFF, that detect movement of visual images. To understand the roles of these cells in controlling eye movements, we studied the optokinetic responses (OKRs) of mutant mice with dysfunctional ON‐bipolar cells that have a functional obstruction of transmission to ON direction‐selective ganglion cells. Experiments were carried out to examine the initial and late phases of OKRs. The initial phase was examined by measurement of eye velocity using stimuli of sinusoidal grating patterns of various spatiotemporal frequencies that moved for 0.5 s. The mutant mice showed significant initial OKRs, although the range of spatiotemporal frequencies that elicited these OKRs was limited and the response magnitude was weaker than that in wild‐type mice. To examine the late phase of the OKRs, the same visual patterns were moved for 30 s to induce alternating slow and quick eye movements (optokinetic nystagmus) and the slow‐phase eye velocity was measured. Wild‐type mice showed significant late OKRs with a stimulus in an appropriate range of spatiotemporal frequencies (0.0625–0.25 cycles/°, 0.75–3.0 Hz, 3–48°/s), but mutant mice did not show late OKRs in response to the same visual stimuli. The results suggest that two groups of direction‐selective ganglion cells play different roles in OKRs: ON direction‐selective ganglion cells contribute to both initial and late OKRs, whereas ON–OFF direction‐selective ganglion cells contribute to OKRs only transiently.

The Initial Disparity Vergence Elicited With Single and Dual Grating Stimuli in Monkeys: Evidence for Disparity Energy Sensing and Nonlinear Interactions

We recorded the initial vertical vergence eye movements elicited in monkeys at short latency ( approximately 70 ms) when the two eyes see one-dimensional (1D) horizontal grating patterns that are identical except for a phase difference (disparity) of one-quarter wavelength. With gratings composed of single sine waves, responses were always compensatory, showing Gaussian dependence on log spatial frequency (on average: peak = 0.75 cycles/deg; SD = 0.74; r(2) = 0.980) and monotonic dependence on log contrast with a gradual saturation well described by the Naka-Rushton equation (on average: n = 0.89; C(50) = 4.1%; r(2) = 0.978). With gratings composed of two sine waves whose spatial frequencies were in the ratio 3:5 and whose disparities were of opposite sign (the 3f5f stimulus), responses were determined by the disparities and contrasts of the two sine-wave components rather than the disparity of the features, consistent with early spatial filtering of the monocular inputs before their binocular combination and mediation by detectors sensitive to disparity energy. In addition, responses to the 3f5f stimulus showed a nonlinear dependence on the relative contrasts of the two sine waves. Thus on average, when the contrast of one sine wave was 2.3 times greater than that of the other, the one with the lower contrast was largely ineffective as though suppressed, and responses were determined almost entirely by the sine wave of higher contrast: Winner-Take-All. These findings are very similar to those published previously on the vertical vergence responses of humans, indicating that the monkey provides a good animal model for studying these disparity vergence responses.

Distribution of optokinetic sensitivity across the retina of mice in relation to eye orientation.

We examined the effects of stimulus size and location on the mouse optokinetic response (OKR). To this end, we recorded initial OKRs elicited by a brief presentation of horizontally moving grating patterns of different vertical widths and locations in the visual field. Large-field stimuli generated large sustained OKRs, whereas visual stimuli of narrower vertical widths elicited weaker sustained responses at the later period (400-500 ms after the onset of stimulus motion). However, even stimuli of only 5 degrees vertical width elicited detectable transient responses at the initial open-loop period (100-200 ms after the onset of stimulus motion). Presenting 5 degrees -width stimuli at different vertical locations (-10 degrees to +35 degrees relative to the horizon) revealed the spatial distribution of optokinetic sensitivity across the retina. The most sensitive part of the visual field was located at +25 degrees . In addition, we examined the vertical orientation of the eye under our stereotaxic set-up. We observed the optic disc using a hand-held fundus camera and determined the ocular orientation. All eye orientations were distributed in the range of +20-30 degrees relative to the horizon (25.2+/-2.5 degrees ). Thus, the direction of the most sensitive visual field matched the angle of eye orientation. These findings indicate that the spatial distribution of visual field sensitivity to optokinetic stimuli coincides with the distribution of retinal ganglion cell density.

Principal Fourier component of motion stimulus dominates the initial optokinetic response in mice.

Optokinetic responses (OKRs) are reflexive eye movements elicited by a moving visual pattern, and have been recognized in a variety of species. Several brainstem and cortical structures are known to be implicated in the generation of OKRs in primates, while the OKRs of afoveate mammals have been posited to be dominated by subcortical structures. To understand the subcortical mechanism underlying OKRs, the initial OKRs to horizontal quarter-wavelength steps applied to vertical grating patterns were studied in adult C57BL/6J mice under the monocular viewing conditions. The initial OKRs to sinusoidal gratings showed directional asymmetry with temporal-to-nasal predominance, a common characteristic of afoveate mammals that uses the subcortical structures to elicit OKRs. We then examined whether the OKRs of afoveate mammals are driven by the same visual features of the moving images as those in primates. The OKRs in mice were elicited by using the missing fundamental (mf) stimuli and its variants that had been used to understand the mechanism(s) underlying the cortical control of eye movements in primates. We obtained the results indicating that the OKRs of mice are driven by the principal Fourier component of moving visual image as in primates despite the differences in neural circuitries.

Role of the Mouse Retinal Photoreceptor Ribbon Synapse in Visual Motion Processing for Optokinetic Responses

The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs). The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz) that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz). The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz) were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz). These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated.