We varied the amplitude from 20 to 120 in steps of 10 while stimulating under optimal conditions, (stimulus velocity = 12/s, spatial frequency = 0.2 cycle/, contrast = 1). 3D and and4C).4C). We had previously reported complete loss of vertical OKR in Brn3bKO/KO mice (Badea et al. In the present work we (1) describe the design of a novel OKR test apparatus in which a rotating computer-controlled projector delivers diverse and easily generated OKR stimuli, and (2) use infrared imaging to monitor the murine OKR and then quantify the number of ETMs per unit time in a rapid, objective, and reproducible manner. This difference in head inclination around the pitch axis could result in an enlarged binocular field of view contribution to the OMR compared with the OKR, and reorientation of the eyes relative to the head as a result of the maculo-ocular tilt reflex (Maruta et al. Click through the PLOS taxonomy to find articles in your field. 3D and and4B;4B; 12 tracking phases per minute, and hence 1 tracking phase for each of the 12 5-s trial segments). 4F) also show very similar spatial frequency fit curves (Fig. In animals that lack a fovea, such as mice, the gain is typically less than unity, with the result that the image is not fully stabilized on the retina. At present, one of the major challenges in CNS drug development is the establishment of quantitative and high throughput animal tests that can be used to narrow a large numbers of candidate compounds for clinical testing. I asked her if she wanted to see a psychiatrist. Within the free iPhone app Eye Handbook, theres an OKN drum animation. One variation on the rotating cylinder method uses a non-rotating cylinder illuminated from above by light that passes through numerous small holes in a slowly rotating screen; the resulting pattern of light and shadow rotates around the inner face of the cylinder [35]. If we make the simplifying assumption that the relevant genes segregate randomly, are codominant, and are of equal effect, then the number of genes is readily estimated by comparing the observed distribution of ETMs in the F2 cohort to the calculated distribution of C57BL/6J and 129/SvEv alleles in the F2 generation [50]. interpreted results of experiments; F.K., M.T., and T.C.B. In mice with other genotypes, the intrinsic pupil constriction with photopic stimuli was sufficient for accurate measurements of pupil position. The two eyes perform synchronized tracking phases, followed by fast reset phases, whereas the head moves in stimulus direction at a very low gain. The same animal was not measured again until it had rested at least 2 h. Recordings were then analyzed semiautomatically. Under full field stimulation (mask 1), 36 tracking phases per minute (median) are detected for either stimulus direction. (A) Contrast sensitivity. A system to measure the optokinetic and optomotor response in mice. This operation creates stripes with contrasts ranging from 0% to 100% without changing the average luminance of the stimulus. Yes Patient positioning was individualized to maximally challenge balance while still being sustainable by the patient. (C) ETMs per 30 second interval vs. the relative velocity of the slow component for C57BL/6J and 129/SvEv. Compensatory increase of the cervico-ocular reflex with age in healthy The optokinetic reflex causes eye movement in response to objects moving in the periphery while the head is stationary. Image stabilization, noted above in the context of the head turning reflex, is predominantly mediated by two types of oculomotor responses: the optokinetic reflex (OKR; also called optokinetic nystagmus or OKN) and the vestibulo-ocular reflex (VOR)[15], [16]. The mice typically awoke 3060 minutes after surgery and were monitored for feeding, grooming, and gait. The stimulus is controlled by a laptop computer and a projector, both of which sit approximately two meters above the drum on a rotating table that is controlled by a variable speed motor (not shown). Figure 4J shows the fit curves for OKR gain, number and duration of tracking phases, and number of reset phases, corresponding to data in Fig. With the goal of making the mouse OKR a more accessible, versatile, and rapid test of CNS function, the present study describes a series of modifications of the test apparatus, visual stimulus, and data analysis, and applies these approaches to the quantification of genetic variation and CNS drug action. An electric motor (Dayton; Niles, IL; Part Number: 4Z525A) controlled by a DC Speed Control (Dayton) rotated the stage. The holder was then positioned in the center of the setup and the virtual sphere (Fig. 6, C, D, F, and G). and T.C.B. The OKR is induced when the entire visual scene drifts across the retina, eliciting eye rotation in the same direction and at a velocity that minimizes the motion of the image on the retina. Mice alternate between type I responses, consisting of low-gain, continuous head tracking phases in stimulus direction, amounting to small angular excursions and uninterrupted by reset phases, and type II responses, consisting of shorter, faster head tracking phases that are followed by reset phases, essentially resembling classic OKR eye movements (equivalent to a head nystagmus). The number of animals tested, and the means and standard deviations are indicated for each distribution. The Optokinetic Uncover Test | SpringerLink Most OKR movements are performed at 10/s, last 800 ms (median), and are followed by a fast reset movement (Fig. 7E). Hence, mice perform most head and eye tracking phases at velocities of 1014/s, and determining the number of individual tracking phases results in a bell-shaped curve around this optimum. Similar gain dependencies on stimulus velocities for head and eye movements have been previously reported for rabbits, guinea pigs, and rats (Collewijn 1969, 1977; Fuller 1985, 1987; Gresty 1975). 7E). Dental cement (a 1:1 mixture of methyl methacrylate and diethyl phthalate; Lang Dental; Wheeling,IL, Part Number: 60090) was mixed and added drop-wise to the top of the skull to cover the metal screws. Commercial software (ISCAN) was used to monitor the positions of (1) the pupil, the principal sink for both visible and infrared radiation, and (2) the point of reflection of incident infrared radiation at the surface of the cornea. In contrast, participation during OMR (under the same stimulus conditions) is far less consistent; i.e., the amount of time the mouse spends engaging in OMR events is reduced and highly variable (see Figs. We also systematically recorded OKR responses at various spatial frequencies under the same stimulus conditions as for OMR in Brn3bWT/WT and Brn3bKO/KO animals. Present address of F. Kretschmer: Scientific Computing Facility, Rm. Although the OKR is conjugate, it has previously been reported that monocular stimulation in the temporal nasal (T-N) direction relative to the stimulated eye is more effective (Cahill and Nathans 2008; Stahl et al. Although OKR signal-to-noise ratios are much better, we show that OMR can yield similar results without the need for invasive procedure, fixation of the animal, or calibration procedures. The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. To assess the mode of inheritance of saccade frequency, nine C57BL/6J mice, nine 129/SvEv mice, eight C57BL/6J129/SvEv F1 mice, and 74 F2 mice (derived by intercrossing the F1 mice) were tested to determine the maximal number of ETMs per 30-second interval (from among 16 such intervals per mouse) using the standard OKR stimulus (Figure 7). PLOS ONE promises fair, rigorous peer review, Intuitively, losing individual ON-DS RGCs will result in reduced response strength (number of movements and gain) but should only affect spatial frequency tuning after extensive RGC loss, because each individual ON-DS cell can detect the movement, and the whole retina would have to lose a large number of ON-DS RGCs before the edges of the pattern would fall on tissue devoid of detectors. The absolute value of head or eye velocity, as well as the customary ranges for head and eye excursions during OMR and OKR, are probably more related to the kinematic properties of the systems subserving them (head and neck muscles, oculomotor muscles, interactions with vestibular and proprioceptive systems, etc.). Genetic dissection of retinal inputs to brainstem nuclei controlling image stabilization, Resetting fast phases of head and eye and their linkage in the frog, Development of the optokinetic response in macaques: a comparison with cat and man, Observations on monocular deprivation in mice, Optokinetic reactions in man elicited by localized retinal motion stimuli. Optokinetic Response - an overview | ScienceDirect Topics The optokinetic reflex causes eyes to drift horizontally from side-to-side for example, as we watch the scenery through a window of a moving train. Under optimal OMR stimulus conditions (photopic light levels, contrast = 1, stimulus angular speed = 12/s, spatial frequency = 0.2 cycle/), OMR in wild-type (Brn3bWT/WT) mice can alternate between continuous tracking phases in stimulus direction (Fig. These reflexes elicit compensatory head movements (optomotor response, OMR) in unrestrained animals or compensatory eye movements (optokinetic response, OKR) in head-fixed or unrestrained animals exposed to globally rotating striped patterns. We note that type I tracking (slow) phases can also be seen for head-fixed OKR, predominantly under suboptimal stimulus conditions. We note that, in our recordings, head OMR events have strong translational components, and hence are more easily recognized by projections onto the orthogonal axes (Fig. Spectral composition and relative intensities of OKR stimuli used for chromatic vs. gray scale experiments. The authors thank Terry Shelley for building the rotating projector platform; Chris O'Donnell, John Stahl, and David Yue, for advice on headposting mice, the mouse OKR, and data analysis, respectively; Martin Biel, Samer Hattar, Janice Lem, Yanshu Wang, and King-wai Yau for knockout or transgenic mice; Jiangyang Zhang and Susumu Mori for performing the MRI analysis; David Yue and John Stahl for advice; Tim Phelps for producing Figure 1A; and Tudor Badea, Chunqiao Liu, Americo Migliaccio, Amir Rattner, Randall Reed, and David Zee for helpful comments on the manuscript. No head retractions/resets could be observed. (C) Angular velocity. I explained that wed be starting an IV, getting labs, ordering a head CT if she werent more awake soon. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, For sequential surgeries, instruments were sterilized between mice by immersion in Cidex (Advanced Sterilization Products; Miami, FL; Part Number: 2245). Consistent with a conjugate response, the OKR is nulled by symmetric binocular temporal-to-nasal or nasal-to-temporal motion (delivered by projecting a movie, since mirror symmetric stimuli cannot be produced by rotating the projector; Figure 6A, lines 3 and 4). Basic visual response properties, Acting without seeing: eye movements reveal visual processing without awareness, Eye movements of the murine P/Q calcium channel mutant rocker, and the impact of aging, Using eye movements to assess brain function in mice. The optokinetic reflex (OKR) responds to visual motion stimulation. The effects of the left or right monocular hemifield occlusions were even more pronounced, reducing the number of OKR phases to almost half compared with the unmasked condition, under either T-N or N-T stimulation. The vestibulo-ocular reflex ( VOR) is a reflex acting to stabilize gaze during head movement, with eye movement due to activation of the vestibular system. This can be reproduced by spinning an OKN drum directly in front of a patient. 7A), represented by the area centered around vertical meridian 0 and delimited by the horizontal meridian at 30 and the two gray monocular regions, is relatively small. Functional architecture of an optic flow-responsive area that drives horizontal eye movements in zebrafish, Orienting otolith-ocular reflexes in the rabbit during static and dynamic tilts and off-vertical axis rotation, Eye-neck coupling during optokinetic responses in head-fixed pigeons (Columba livia): influence of the flying behaviour, Perceptual rivalry: reflexes reveal the gradual nature of visual awareness, Eye orientation during static tilts and its relationship to spontaneous head pitch in the laboratory mouse. Whereas the maximal amplitudes for all other contrast levels were diminished, differences from those observed in Brn3bWT/WT littermates were not significant. As a test of the sensitivity and specificity of the OKR to variations in underlying physiologic parameters, we systematically explored the response to scotopic or photopic light levels (average stimulus intensities of 0.3 lux or 200 lux, respectively) in a variety of mutant mice in which rods, cones, or intrinsically photosensitive retinal ganglion cells (ipRGCs) were eliminated or inactivated individually or in various combinations (Figure 3). 4, AH, to directly compare the qualitative trends in the different parameters of the responses. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, Umino Y, Herrmann R, Chen CK, Barlow RB, Arshavsky VY, Solessio E. The relationship between slow photoresponse recovery rate and temporal resolution of vision, Speed, spatial, and temporal tuning of rod and cone vision in mouse, The dynamic characteristics of the mouse horizontal vestibulo-ocular and optokinetic response, Age- and sex-related differences in contrast sensitivity in C57BL/6 mice, Three-dimensional optokinetic eye movements in the C57BL/6J mouse, Control of human optokinetic nystagmus by the central and peripheral retina: effects of partial visual field masking, scotopic vision and central retinal scotomata. Eye movements of the murine P/Q calcium channel mutant tottering, and the impact of aging, A comparison of video and magnetic search coil recordings of mouse eye movements. For each mouse, the OKR was recorded before and >24 hours after drug exposure using the standard 30 seconds on/30 seconds off OKR stimulus paradigm (Figure 2) with alternating clockwise and counterclockwise rotation. 5, C and F). Data are from the experiment shown in Figure 5A. How much of the unconscious is just pre-threshold? Be that as it may, the angular excursions for the two eyes relative to the head are comparatively well synchronized (Fig. Ups and downs of optokinetic nystagmus - British Journal of Ophthalmology (A) The mouse is held in a horizontal acrylic cylinder within a large cylindrical drum. The optokinetic reflex allows us to follow objects in motion when the head remains stationary. We recorded each animal for at most 30 min and interrupted recordings for at least 5 min, allowing us to clean the mirrors and platform. (D) IR image of a mouse eye showing the pupil (large upper right white circle with centered cross) and the corneal reflection (lower left white circle with centered cross). 4, DF). The ISCAN software has assigned the IR sink as the pupil and the IR peak as the corneal reflection. The image was rotated at 5 per second. In control experiments, IP injection of saline produced no changes in the OKR. 2015). The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. Experiments were performed at a stimulus angular speed of 12/s (Fig. Substantial variations have been reported in OKR response amplitudes in various inbred strains of mice [20], [21]. An empirical approach to determining this proportionality can be found in Sakatani and Isa [26]. The test can be repeated; you may have to hold the eyelids up in order to see the downward eye movement clearly. 2010). We have used this system to (1) define the basic OKR stimulus-response characteristics of C57BL/6J and 129/SvEv and of genetically engineered variants that lack one or more photoreceptor systems or that have an altered spectral sensitivity, (2) show that the characteristic difference in OKR frequency between C57BL/6J and 129/SvEv is inherited as a polygenic trait, and (3) demonstrate that the mouse OKR can be used as a sensitive and quantitative assay for drug action in the CNS. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For these experiments, rod, cone or ipRGC function was individually eliminated by targeted disruption of the genes coding for, respectively, rod transducin-alpha (Gnat1)[37], one of the two cone cyclic nucleotide gated channel subunits (Cng3)[38], or melanopsin, the ipRGC-specific opsin (Opn4)[39]. No response. . Unless otherwise indicated the stimulus parameters match those shown in Figure 2. Yes Citation: Cahill H, Nathans J (2008) The Optokinetic Reflex as a Tool for Quantitative Analyses of Nervous System Function in Mice: Application to Genetic and Drug-Induced Variation. In addition, if RGCs projecting to LGN or SC could drive a hypothetical alternative circuit, they should be able to do so for the vertical OKR component, which is not what we observed (Fig. In rodents, the lateral placement of the eyes provides a visual field that subtends 270 in the horizontal plane. Unless otherwise stated, OKR stimuli were presented as alternating 30-second intervals of moving black and white stripes and of a uniform grey. We have focused on the number of ETMs per unit time because this parameter is relatively insensitive to changes in the shape of the slow component of the OKR, and it is easily quantified by automated procedures based on the first derivative of eye position with respect to time or with a neural network (Figure 2A and data not shown); it is also easily quantified by visual inspection. To compare the basic response properties of the OKR between C57BL/6J and 129/SvEv, we have analyzed the effect of contrast, spatial frequency, angular velocity, monocular vs. binocular presentation, and direction of rotation, in each case quantifying the OKR response by determining the average number of ETMs per 30-second stimulus interval. Tracking movements covering the entire unidirectional stimulation epoch become less and less frequent as the stimulus angular amplitude increases from 20 to 120, and gradually get replaced by the more stereotypical short tracking phases covering the customary range of 3.55. The series of OKR responses shown in Figure 5C also illustrates the characteristic saccade-to-saccade variability of the C57BL/6J OKR, a variability that becomes more pronounced with suboptimal stimuli. The OKR offers only a few parameters for quantitative evaluation, including the number of eye tracking movements (ETMs) per unit time and the gain (the angular velocity of the eye relative to the angular velocity of the stimulus).
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optokinetic reflex test