Ocular motor abnormalities in achiasmatic mutant Belgian sheepdogs: Unyoked eye movements in a mammal

Mutations in the gene encoding the ion pore of the P/Q voltage-activated calcium channel (CACNA1A) are predicted to alter synaptic transmission and dendritic excitability within cerebellar granule and Purkinje cells. Determining the relationships between these alterations, neuronal activity, and behavior may yield insight into the relationship between neuronal intrinsic properties and signal processing within the ocular motor system. Toward this end, we compared ocular motor performance in the CACNA1A mutant rocker and C57BL/6 controls. Average vertical eye position was abnormally elevated in the mutants, a finding that may be analogous to downbeat nystagmus seen in human cerebellar disorders. Fast phases of vestibular nystagmus were slowed by approximately 18% of control values. The angular vestibuloocular reflex (VOR) in darkness and light (visual VOR, or VVOR), assessed at 0.1–1.6 Hz, exhibited subnormal gains at the highest stimulus frequencies and increased phase leads at the lowest stimulus frequencies. Horizontal optokinetic responses to constant velocity drum rotation of ±2.5–40°/s exhibited minimally reduced gains. Attempts to increase VOR gain by concomitant optokinetic and vestibular stimulation were confounded by the tendency of the mice to habituate to repetitive vestibular stimulation, but attempts to induce coupling of vertical eye movements to horizontal vestibular stimulation (cross-axis adaptation) generated rapid plastic changes in controls and little effect in mutants. With the notable exceptions of the vertical elevation and optokinetic gains, the ocular motor abnormalities were stable over a broad range of animal age, a result compatible with the abnormalities arising as direct consequences of the inborn alteration in calcium channel biophysics.

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Disorders of Ocular Motility with Disease Affecting the Basal Ganglia, Cerebral Cortex, and in Systemic Conditions

The Neurology of Eye Movements ◽

10.1093/med/9780199969289.003.0014 ◽

2015 ◽

pp. 916-1024

Author(s):

R. John Leigh ◽

David S. Zee

Keyword(s):

Eye Movements ◽

Basal Ganglia ◽

Bipolar Affective Disorder ◽

Ocular Motility ◽

Ocular Motor ◽

Psychiatric Illnesses ◽

Tay Sachs Disease ◽

Motor Apraxia ◽

Niemann Pick ◽

Eye Movement Disorders

This chapter reviews (with illustrative videos) disorders of gaze in diseases involving the basal ganglia, including Parkinson’s disease, progressive supranuclear palsy (PSP), hyperkinetic movement syndromes such as oculogyric crisis, and Huntington’s disease. Ocular motor syndromes caused by lesions in the cerebral hemispheres are discussed, including gaze deviations. Distinctive features of ocular motor apraxia, both acquired and congenital, are highlighted. Eye movements during epilepsy, and abnormal eye movements in patients with dementia, including Alzheimer’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis are reviewed. Eye movement disorders in psychiatric illnesses, including schizophrenia, bipolar affective disorder, and autism are summarized. Eye movements in stupor and coma are discussed. The range of ocular motor disturbances in multiple sclerosis (MS) is reviewed as well as the ocular motor manifestations of metabolic and deficiency disorders, including Niemann-Pick disease, Tay-Sachs disease, Gaucher’s disease, and Wernicke’s encephalopathy. Disorders of eye movements induced by drugs or toxins are tabulated.

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Eye Movements of the Murine P/Q Calcium Channel Mutant Tottering, and the Impact of Aging

Journal of Neurophysiology ◽

10.1152/jn.00318.2005 ◽

2006 ◽

Vol 95 (3) ◽

pp. 1588-1607 ◽

Cited By ~ 37

Author(s):

John S. Stahl ◽

Robert A. James ◽

Brian S. Oommen ◽

Freek E. Hoebeek ◽

Chris I. De Zeeuw

Keyword(s):

Eye Movements ◽

Calcium Channel ◽

Motor Behavior ◽

Motor Deficits ◽

Ocular Motor ◽

Gene Encoding ◽

Optokinetic Reflex ◽

Behavioral Abnormalities ◽

Cross Axis ◽

The Impact

Mice carrying mutations of the gene encoding the ion pore of the P/Q calcium channel (Cacna1a) are an instance in which cerebellar dysfunction may be attributable to altered electrophysiology and thus provide an opportunity to study how neuronal intrinsic properties dictate signal processing in the ocular motor system. P/Q channel mutations can engender multiple effects at the single neuron, circuit, and behavioral levels; correlating physiological and behavioral abnormalities in multiple allelic strains will ultimately facilitate determining which alterations of physiology are responsible for specific behavioral aberrations. We used videooculography to quantify ocular motor behavior in tottering mutants aged 3 mo to 2 yr and compared their performance to data previously obtained in the allelic mutant rocker and C57BL/6 controls. Tottering mutants shared numerous abnormalities with rocker, including upward deviation of the eyes at rest, increased vestibuloocular reflex (VOR) phase lead at low stimulus frequencies, reduced VOR gain at high stimulus frequencies, reduced gain of the horizontal and vertical optokinetic reflex, reduced time constants of the neural integrator, and reduced plasticity of the VOR as assessed in a cross-axis training paradigm. Unlike rocker, young tottering mutants exhibited normal peak velocities of nystagmus fast phases, arguing against a role for neuromuscular transmission defects in the attenuation of compensatory eye movements. Tottering also differed by exhibiting directional asymmetries of the gains of optokinetic reflexes. The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains.

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Aetiological Factors in Dyslexia: II. Ocular-Motor Programming

Perceptual and Motor Skills ◽

10.2466/pms.1978.47.2.667 ◽

1978 ◽

Vol 47 (2) ◽

pp. 667-672 ◽

Cited By ~ 7

Author(s):

Gerald Leisman ◽

Maureen Ashkenazi ◽

Lance Sprung ◽

Joddy Schwartz

Keyword(s):

Eye Movements ◽

Saccadic Eye Movements ◽

Motor Programming ◽

Ocular Motor

A study is presented in which the preprogramming of saccadic eye movements is examined in normal (16 boys, 4 girls) and dyslexic subjects (19 boys, 1 girl), as well as the patterning of ocular-motor differences between subjects, which is consistent with the previous study in which no differences in saccadic control are demonstrated between groups of subjects.

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Cerebellar vermis hypoplasia - non progressive congenital ataxia: clinical and radiological findings in a pair of siblings

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2000000500016 ◽

2000 ◽

Vol 58 (3B) ◽

pp. 897-900 ◽

Cited By ~ 2

Author(s):

ISAC BRUCK ◽

SÉRGIO A. ANTONIUK ◽

ARNOLFO DE CARVALHO NETO ◽

ADRIANE SPESSATTO

Keyword(s):

Differential Diagnosis ◽

Correct Answer ◽

Radiological Finding ◽

Cerebellar Atrophy ◽

Cerebellar Vermis ◽

Ocular Motor ◽

Radiological Findings ◽

Motor Delay ◽

Familial Cases ◽

Motor Abnormalities

We describe the clinical and radiological findings of a pair of siblings with cerebellar vermis hypoplasia and compare them with the literature. Both of them present pregnancies and deliveries uneventful and both presented some grade of hypotonia, ataxia, ocular motor abnormalities and mild motor delay and slurred speech. These siblings meet many of the criteria described in non-progressive congenital ataxia in which can occur familial cases with cerebellar atrophy, including vermis hypoplasia. As differential diagnosis we compare them with related syndromes and with Joubert's syndrome which main radiological finding on MRI is vermis hypoplasia associated with "molar tooth" appearance. The correct answer for these cases will only be possible by molecular genetics.

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Ocular motor abnormalities in Huntington's disease

Vision Research ◽

10.1016/s0042-6989(96)00169-1 ◽

1997 ◽

Vol 37 (24) ◽

pp. 3639-3645 ◽

Cited By ~ 104

Author(s):

Adrian G. Lasker ◽

David S. Zee

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Ocular Motor ◽

Motor Abnormalities

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Disconjugate Eye Movements during Electronystagmographic Testing in Patients with Known Central Nervous System Lesions

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348947508400314 ◽

1975 ◽

Vol 84 (3) ◽

pp. 368-373

Author(s):

Joseph Kimm ◽

James B. MacLean

Keyword(s):

Central Nervous System ◽

Eye Movements ◽

Eye Movement ◽

Motor System ◽

Treatment Plan ◽

Medial Longitudinal Fasciculus ◽

Ocular Motor ◽

Measuring Techniques ◽

Ocular Motor System ◽

Cns Lesions

A tacit assumption underlying current ENG testing is that the eyes move conjugately. However, considering the intricate neuroanatomical pathways within the ocular motor system in addition to the elaborate vestibulo-ocular connections, we think it reasonable that disconjugate eye movements may result with certain CNS lesions. Recently we have employed independent eye movement measuring techniques in order to assess the movement of each eye separately during our ENG valuations. The preliminary work has revealed that disconjugate eye movements occurred even with extra-axial lesions which spared the medial longitudinal fasciculus. These data may be valuable for the neurotologist with regard to differential diagnosis and prescription of a treatment plan for the patient. The eye movement patterns of patients with confirmed CNS lesions and other interesting findings are presented.

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Visually induced adaptive changes in primate saccadic oculomotor control signals

Journal of Neurophysiology ◽

10.1152/jn.1985.54.4.940 ◽

1985 ◽

Vol 54 (4) ◽

pp. 940-958 ◽

Cited By ~ 94

Author(s):

L. M. Optican ◽

F. A. Miles

Keyword(s):

Eye Movements ◽

Time Constant ◽

Retinal Image ◽

Prolonged Exposure ◽

Oculomotor Control ◽

Motor Deficits ◽

Ocular Motor ◽

Retinal Slip ◽

Full Field ◽

Adaptive Changes

Saccades are the rapid eye movements used to change visual fixation. Normal saccades end abruptly with very little postsaccadic ocular drift, but acute ocular motor deficits can cause the eyes to drift appreciably after a saccade. Previous studies in both patients and monkeys with peripheral ocular motor deficits have demonstrated that the brain can suppress such postsaccadic drifts. Ocular drift might be suppressed in response to visual and/or proprioceptive feedback of position and/or velocity errors. This study attempts to characterize the adaptive mechanism for suppression of postsaccadic drift. The responses of seven rhesus monkeys were studied to postsaccadic retinal slip induced by horizontal exponential movements of a full-field stimulus. After several hours of saccade-related retinal image slip, the eye movements of the monkeys developed a zero-latency, compensatory postsaccadic ocular drift. This ocular drift was still evident in the dark, although smaller (typically 15% of the amplitude of the antecedent saccade, up to a maximum drift of 8 degrees). Retinal slip alone, without a net displacement of the image, was sufficient to elicit these adaptive changes, and compensation for leftward and rightward saccades was independent. It took several days to complete adaptation, but recovery (in the light) was much quicker. The decay of this adaptation in darkness was very slow; after 3 days the ocular drift was reduced by less than 50%. The time constants of single exponential curve fits to adaptation time courses of data from five animals were 35 h for acquisition, 4 h for recovery, and at least 40 h for decay in darkness. Descriptions of the central innervation for a saccade are usually simplified to only two components: a pulse and a step. It has been hypothesized that suppression of pathological postsaccadic drift is achieved by adjusting the ratio of the pulse to the step of innervation (19, 26). However, we show that the time constant of the ocular drift is influenced by the time constant of the adapting stimulus, which cannot be explained by the simple pulse-step model of saccadic innervation. A more realistic representation of the saccadic innervation has three components: a pulse, an exponential slide, and a step. Normal saccades were accurately simulated by a fourth-order, linear model of the ocular motor plant driven by such a pulse-slide-step combination. Saccades made after prolonged exposure to optically induced retinal image slip could also be simulated by properly adjusting the slide and step components.(ABSTRACT TRUNCATED AT 400 WORDS)

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