the contents by NLM or the National Institutes of Health. Reflexes and the Eye - EyeWiki Indeed, there is no mention of it in the standard reference book on mouse behavioral phenotyping [6] or in standard compendia of mouse neurologic tests [31]. Recordings from the lateral camera were synchronized to the recordings of the camera monitoring the animal from the top. Finally, we demonstrate the sensitivity and high temporal resolution of the OKR for quantitative analysis of CNS drug action. 1Aiv), is calculated (Kretschmer et al. Here we define an ETM as one slow tracking movement followed by one saccade, and we quantify the ETMs by counting the number of saccades. The OKR has gained popularity in studies of neuronal circuits [81], [94], [95], [96]. We used fourth-order polynomial functions as optimal fits for the Brn3bWT/WT data shown in Fig. 5, D and E). a moving object are called optokinetic nystagmus; nystagmus itself is the involuntary movement of the eye back and forth, up and down, or in a rotatory or a mixed fashion.) 4E, around 6 per minute, or only 1 every other 5-s unidirectional stimulus epoch) and lasted only ~4 s (Fig. We therefore measured vertical eye movements in response to a stimulus presented on a virtual sphere rotated around the roll axis (Fig. At an amplitude of 20, the animal manages to follow the stimulus for the entire duration of one epoch (20 divided by 12/s = 1,666 ms) on most trials. Under scotopic conditions, the threshold values range between 0.43 and 0.31 cycle/ for contrast levels 10.05 (Fig. Standard anatomical and visual space for the mouse retina: computational reconstruction and transformation of flattened retinae with the Retistruct package. PDF ASSESSMENT: VESTIBULAR TESTING TECHNIQUES IN ADULTS AND - Neurology 4, DF). 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. Case One underwent 9 treatments of traditional vestibular and balance retraining with modest response. To initiate an experiment, 75 mg/kg ketamine was administered by IP injection, and the mouse was immediately transferred to the recording chamber to begin measuring the OKR. Yes Eye rotation is calculated based on a simplified model that places both the pupil image and the corneal reflections at the surface of the globe and assumes rotation about the center of a spherical globe (see Results section). The Optokinetic Reflex as a Tool for Quantitative Analyses of - PLOS (B) Quantifying the number of ETMs/30 seconds for the stimuli tested in panel (A). 4G), the manually annotated number of tracking phases (Fig. 2, A, C, E, and G). For example, the OKR could be used to quantify drug-induced sedation or arousal, or to monitor the progression or the therapeutic response of neurodegenerative disease. 3A, top two traces). A best fitting straight line is superimposed. Optokinetic Nystagmus (normal physiological occurrence of nystagmus under these conditions) Nystagmus should beat in opposite direction to the In mice with other genotypes, the intrinsic pupil constriction with photopic stimuli was sufficient for accurate measurements of pupil position. Consistent with this observation, ablating cones with diphtheria toxin, while leaving the ipRGC system intact, does not eliminate the photopic OKR (Figure 3A, line 7) unless rod function is eliminated (Figure 3A, line 8) or the pupils are dilated pharmacologically (data not shown). Figure 8, A and B, shows exemplary traces of head and eye movements recorded simultaneously under optimal stimulation conditions. The optokinetic response (OKR) describes the preference of the fish to move its eyes in the direction of perceived motion and is the first visual behavior in the larva that requires form vision. https://doi.org/10.1371/journal.pone.0002055.g005. An argument for alternative RGCs being involved is that the type I movements are also present in wild-type mice, at suboptimal but also optimal stimulation conditions. The OKR reaches its steady state form within one second of the onset of stimulus motion and it shows no adaptation over more than 20 minutes of continuous stimulation, an interval that encompasses over 600 ETMs (Figure 2B). The scotopic maximal OMRind amplitudes are somewhat (not statistically significant) lower than the photopic amplitudes (e.g., at spatial frequency = 0.2, P values at contrast levels 1, 0.2, 0.15, and 0.1 are 0.2330, 0.0518, 0.4232, and 0.6208, respectively). The gain of horizontal OKR tracking (slow) phases is dramatically affected, and Brn3bKO/KO OKR events consist of essentially continuous, low-gain tracking uninterrupted by reset (fast) phases (as shown in examples in Fig. I told her to tell me when she was thirsty so that I could give her some water or juice. Optokinetic Reflex - an overview | ScienceDirect Topics 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). Address for reprint requests and other correspondence: T. C. Badea, Retinal Circuit Development & Genetics Unit, Neurobiology Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892 (e-mail: Received 2017 Jan 27; Revised 2017 Apr 12; Accepted 2017 Apr 12. 2015 and in this work, Fig. In addition, preclinical CNS drug research could greatly . The histograms in the lower panels of Figure 8A show the distribution of eye positions for the same intervals. As spatial frequencies increased beyond the optimum, the slow phase gain decreased, resulting in OKR movements similar to those seen at 0.05 cycle/. Occlusion of the left (ipsi) eye reduced OKR response in both directions of stimulation (median = 17 phases, mask 6; P = 0.0023 for either T-N or N-T vs. mask 1). The previously reported differences in spatiotemporal tuning for OMR and OKR are a function of the applied metrics (human observer detecting mouse motion for OMR vs. gain for OKR). Analyzed the data: JN HC. Head movements and eye use in chickens. The test can be repeated; you may have to hold the eyelids up in order to see the downward eye movement clearly. True optokinetic nystagmus cannot be induced at the bedside where actually ocular pursuit is being tested. A simple algorithm eliminates many of these artifacts by discounting all supra-threshold first derivative excursions in the correct direction that occur within 470 msecs of a supra-threshold excursion in the wrong direction. Most OKR movements are performed at 10/s, last 800 ms (median), and are followed by a fast reset movement (Fig. We had previously reported complete loss of vertical OKR in Brn3bKO/KO mice (Badea et al. 6, C, D, F, and G). More complex procedures could be devised to quantify variability in ETM shape, timing, and amplitude. All recordings with the lateral camera were done using sine grating stimuli of 0.2 cycle/ spatial frequency rotating at 12/s and changing its direction every 5 s. Mice generate OMR only infrequently during any individual recording period, even under optimal stimulation conditions. 2, A and E), but the polynomial fit was poor (R2 = 0.1955), and most of the curve fit was essentially aligned to the baseline. We note that type I tracking (slow) phases can also be seen for head-fixed OKR, predominantly under suboptimal stimulus conditions. 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. (D) A systematic distortion in the shape of the slow component of the OKR between 45 and 90 seconds after ketamine injection (post-ketamine). Under full field stimulation (mask 1), 36 tracking phases per minute (median) are detected for either stimulus direction. 5, D and E). Relative gain in the slow component of the OKR as a function of percent contrast between the black and white stripes. When the entire image rotates within the drum or, under natural conditions, when a horizontal head turning movement produces a uniform rotation of the entire visual world, the mouse experiences simultaneous nasal-to-temporal stimulus motion in one eye and temporal-to-nasal stimulus motion in the contralateral eye. 6, A and B). 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. Vestibular and oculomotor function in children with CP: Descriptive PLoS ONE 3(4): N, nasal; T, temporal. The VOR is an analogous response to head movement, with input coming from the vestibular system rather than the retina. https://doi.org/10.1371/journal.pone.0002055.g006. Four holes were drilled into the skull, and four 0.93 mm diameter metal screws (Plastics One; Roanoke, VA; Part Number: #8L010121202F) were inserted to provide support. 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. The eye position data file was subject to a local smoothing procedure with the following formula [where xn is the nth eye position measurement (sampled at 60 Hz) and is set to 0.8]: To calculate the standard deviation of eye position in 30 second intervals, the eye position at each time point was further modified by subtracting from it the average eye position over a three second moving window centered on that time point, an operation that largely compensates for any slow background drift in eye orientation. 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). Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, However, unrestrained mice perform OKR-type eye movements, and head gains are very small compared with eye gains, and therefore OMR experiments may miss subtle differences under suboptimal conditions (see Brn3bWT/WT vs. Brn3bKO/KO OMRind comparison at lower contrast values). For OMR, the automated OMRind (Fig. drafted manuscript; F.K., M.T., and T.C.B. 3, quantitated in Fig. To get a better understanding of the range of their variation, we recorded head and eye movements at the reported optimum for OMR (contrast = 1, spatial frequency = 0.2 cycle/, stimulus velocity = 12/s; for OMR: 10 mice were measured 10 times for 1 min; for OKR: 7 mice were measured 3 times for 1 min). (C) ETMs per 30 second interval vs. the relative velocity of the slow component for C57BL/6J and 129/SvEv. A rotating electrical adaptor (Moog; Blacksburg, Virginia) supplied power to the projector. 2, D and K). Sterratt DC, Lyngholm D, Willshaw DJ, Thompson ID. Mice lacking both rod and cone function, with or without functional ipRGCs, show no OKR at any light level (Figure 3A, lines 5 and 6), consistent with the non-image forming nature of the ipRGC signal [41] and previous optomotor behavioral experiments [42].
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