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

2006 ◽  
Vol 95 (3) ◽  
pp. 1588-1607 ◽  
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.

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

2004 ◽  
Vol 91 (5) ◽  
pp. 2066-2078 ◽  
Author(s):  
John S. Stahl
Keyword(s):  
Eye Movements ◽  
Calcium Channel ◽  
Vestibular Stimulation ◽  
Downbeat Nystagmus ◽  
Ocular Motor ◽  
Gene Encoding ◽  
Optokinetic Responses ◽  
Cross Axis ◽  
Motor Abnormalities ◽  
The Impact

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.

Visually induced adaptive changes in primate saccadic oculomotor control signals

1985 ◽  
Vol 54 (4) ◽  
pp. 940-958 ◽  
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)

scholarly journals Locomotion-induced ocular motor behavior in larval Xenopus is developmentally tuned by visuo-vestibular reflexes

2021 ◽  
Author(s):  
Julien Bacqué-Cazenave ◽  
Gilles Courtand ◽  
Mathieu Beraneck ◽  
Hans Straka ◽  
Denis Combes ◽  
...  
Keyword(s):  
Eye Movements ◽  
Motor Behavior ◽  
Pattern Generator ◽  
Efference Copy ◽  
Ocular Motor ◽  
Motor Behaviors ◽  
Locomotor Pattern ◽  
The World ◽  
Neural Computations ◽  
Developmental Switch

Abstract Locomotion requires neural computations to maintain stable perception of the world despite disturbing consequences of the motor behavior on sensory stability. The developmental establishment of locomotor proficiency is therefore accompanied by a concurrent maturation of gaze-stabilizing motor behaviors. Using developing Xenopus larvae, we demonstrate mutual plasticity of predictive spinal locomotor efference copies and multi-sensory motion signals with the aim to constantly ensure dynamically adequate eye movements during swimming. Following simultaneous ontogenetic onsets of locomotion, spino-ocular, optokinetic and otolith-ocular motor behaviors, locomotor efference copy-driven eye movements improve through gradually augmenting influences of semicircular canal signals. Accordingly, neuronal computations change from predominating cancelation of angular vestibulo-ocular reflexes by locomotor efference copies in young larvae to summation of these signals in older larvae. The developmental switch occurs in synchrony with the reduced efficacy of the tail-undulatory locomotor pattern generator causing gradually declining influences on the ocular motor output.

Neural Correlates of Word Recognition: A Systematic Comparison of Natural Reading and Rapid Serial Visual Presentation

2016 ◽  
Vol 28 (9) ◽  
pp. 1374-1391 ◽  
Author(s):  
Benthe Kornrumpf ◽  
Florian Niefind ◽  
Werner Sommer ◽  
Olaf Dimigen
Keyword(s):  
Eye Movements ◽  
Word Recognition ◽  
Rapid Serial Visual Presentation ◽  
Motor Behavior ◽  
Visual Presentation ◽  
Neural Correlates ◽  
Interactive Effects ◽  
Processing Load ◽  
Related Potentials ◽  
The Impact

Neural correlates of word recognition are commonly studied with (rapid) serial visual presentation (RSVP), a condition that eliminates three fundamental properties of natural reading: parafoveal preprocessing, saccade execution, and the fast changes in attentional processing load occurring from fixation to fixation. We combined eye-tracking and EEG to systematically investigate the impact of all three factors on brain-electric activity during reading. Participants read lists of words either actively with eye movements (eliciting fixation-related potentials) or maintained fixation while the text moved passively through foveal vision at a matched pace (RSVP-with-flankers paradigm, eliciting ERPs). The preview of the upcoming word was manipulated by changing the number of parafoveally visible letters. Processing load was varied by presenting words of varying lexical frequency. We found that all three factors have strong interactive effects on the brain's responses to words: Once a word was fixated, occipitotemporal N1 amplitude decreased monotonically with the amount of parafoveal information available during the preceding fixation; hence, the N1 component was markedly attenuated under reading conditions with preview. Importantly, this preview effect was substantially larger during active reading (with saccades) than during passive RSVP with flankers, suggesting that the execution of eye movements facilitates word recognition by increasing parafoveal preprocessing. Lastly, we found that the N1 component elicited by a word also reflects the lexical processing load imposed by the previously inspected word. Together, these results demonstrate that, under more natural conditions, words are recognized in a spatiotemporally distributed and interdependent manner across multiple eye fixations, a process that is mediated by active motor behavior.

scholarly journals Locomotion-induced ocular motor behavior in larval Xenopus is developmentally tuned by visuo-vestibular reflexes

2021 ◽  
Author(s):  
Julien Bacqué-Cazenave ◽  
Gilles Courtand ◽  
Mathieu Beraneck ◽  
Hans Straka ◽  
Denis Combes ◽  
...  
Keyword(s):  
Eye Movements ◽  
Motor Behavior ◽  
Pattern Generator ◽  
Efference Copy ◽  
Ocular Motor ◽  
Motor Behaviors ◽  
Locomotor Pattern ◽  
The World ◽  
Neural Computations ◽  
Developmental Switch

ABSTRACTLocomotion requires neural computations to maintain stable perception of the world despite disturbing consequences of the motor behavior on sensory stability. The developmental establishment of locomotor proficiency is therefore accompanied by a concurrent maturation of gaze-stabilizing motor behaviors. Using developing larval Xenopus, we demonstrate mutual plasticity of predictive spinal locomotor efference copies and multi-sensory motion signals with the aim to constantly ensure dynamically adequate eye movements during swimming. Following simultaneous ontogenetic onsets of locomotion, spino-ocular, optokinetic and otolith-ocular motor behaviors, locomotor efference copy-driven eye movements improve through gradually augmenting influences of semicircular canal signals. Accordingly, neuronal computations change from a predominating cancelation of angular vestibulo-ocular reflexes by locomotor efference copies in young larvae to a summation of these signals in older larvae. The developmental switch occurs in synchrony with a reduced efficacy of the tail-undulatory locomotor pattern generator causing gradually decaying influences on the ocular motor output.

scholarly journals The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites

2021 ◽  
Vol 14 ◽  
pp. 117864692110266
Author(s):  
Yuki Murakami ◽  
Yukio Imamura ◽  
Yoshiyuki Kasahara ◽  
Chihiro Yoshida ◽  
Yuta Momono ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Fetal Brain ◽  
Autism Spectrum ◽  
Maternal Serum ◽  
Fetal Plasma ◽  
Maternal Inflammation ◽  
Interleukin 17A ◽  
Behavioral Abnormalities ◽  
Neuroactive Compounds ◽  
The Impact

Viral infection and chronic maternal inflammation during pregnancy are correlated with a higher prevalence of autism spectrum disorder (ASD). However, the pathoetiology of ASD is not fully understood; moreover, the key molecules that can cross the placenta following maternal inflammation and contribute to the development of ASD have not been identified. Recently, the pro-inflammatory cytokine, interleukin-17A (IL-17A) was identified as a potential mediator of these effects. To investigate the impact of maternal IL-17A on offspring, C57BL/6J dams were injected with IL-17A-expressing plasmids via the tail vein on embryonic day 12.5 (E12.5), and maternal IL-17A was expressed continuously throughout pregnancy. By adulthood, IL-17A-injected offspring exhibited behavioral abnormalities, including social and cognitive defects. Additionally, maternal IL-17A promoted metabolism of the essential amino acid tryptophan, which produces several neuroactive compounds and may affect fetal neurodevelopment. We observed significantly increased levels of kynurenine in maternal serum and fetal plasma. Thus, we investigated the effects of high maternal concentration of kynurenine on offspring by continuously administering mouse dams with kynurenine from E12.5 during gestation. Obviously, maternal kynurenine administration rapidly increased kynurenine levels in the fetal plasma and brain, pointing to the ability of kynurenine to cross the placenta and change the KP metabolites which are affected as neuroactive compounds in the fetal brain. Notably, the offspring of kynurenine-injected mice exhibited behavioral abnormalities similar to those observed in offspring of IL-17A-conditioned mice. Several tryptophan metabolites were significantly altered in the prefrontal cortex of the IL-17A-conditioned and kynurenine-injected adult mice, but not in the hippocampus. Even though we cannot exclude the possibility or other molecules being related to ASD pathogenesis and the presence of a much lower degree of pathway activation, our results suggest that increased kynurenine following maternal inflammation may be a key factor in changing the balance of KP metabolites in fetal brain during neuronal development and represents a therapeutic target for inflammation-induced ASD-like phenotypes.

scholarly journals The Role of Mitochondria in Carcinogenesis

2021 ◽  
Vol 22 (10) ◽  
pp. 5100
Author(s):  
Paulina Kozakiewicz ◽  
Ludmiła Grzybowska-Szatkowska ◽  
Marzanna Ciesielka ◽  
Jolanta Rzymowska
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Dna Polymorphisms ◽  
Gene Encoding ◽  
Dna Mutations ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Gene Coi ◽  
The Impact

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

scholarly journals The Impact of Neonatal Morbidities on Smooth Pursuit Eye Movements in Very Preterm Infants

2011 ◽  
Vol 70 ◽  
pp. 352-352 ◽  
Author(s):  
K Strand Brodd ◽  
K Rosander ◽  
H Grönqvist ◽  
G Holmström ◽  
B Strömberg ◽  
...  
Keyword(s):  
Eye Movements ◽  
Preterm Infants ◽  
Smooth Pursuit ◽  
Smooth Pursuit Eye Movements ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Pursuit Eye Movements ◽  
The Impact

scholarly journals Bedside examination of the vestibular and ocular motor system in patients with acute vertigo or dizziness

2019 ◽  
Vol 3 (2) ◽  
pp. 2514183X1988615
Author(s):  
Alexander A Tarnutzer ◽  
Marianne Dieterich
Keyword(s):  
Diagnostic Testing ◽  
Initial Assessment ◽  
Head Impulse Test ◽  
Motor Deficits ◽  
Ocular Motor ◽  
Bedside Examination ◽  
Life Threatening ◽  
Ocular Motor System ◽  
Bedside Tests ◽  
The Brain

In the initial assessment of the patient with acute vertigo or dizziness, both structured history-taking and a targeted bedside neuro-otological examination are essential for distinguishing potentially life-threatening central vestibular causes from those of benign, self-limited peripheral labyrinthine origin and thus for deciding on further diagnostic testing. In this article, the key elements of the vestibular and ocular motor examination, which should be obtained at the bedside in these acutely dizzy patients, will be discussed. Specifically, this will include the following five domains: ocular stability for (I) nystagmus and for (II) eye position (skew deviation), (III) the head-impulse test (HIT), (IV) postural stability, and (V) ocular motor deficits of saccades, smooth pursuit eye movements, and optokinetic nystagmus. We will also discuss the diagnostic accuracy of specific combinations of these bedside tests (i.e. HIT, testing for nystagmus and vertical divergence, referred to as the H.I.N.T.S. three-step examination), emphasizing that the targeted neuro-otological bedside examination is more sensitive for identifying central causes in acute prolonged vertigo and dizziness than early MRI of the brain.

scholarly journals A test of spatial temporal decoding mechanisms in the superior colliculus

2012 ◽  
Vol 107 (9) ◽  
pp. 2442-2452 ◽  
Author(s):  
Husam A. Katnani ◽  
A. J. Van Opstal ◽  
Neeraj J. Gandhi
Keyword(s):  
Nervous System ◽  
Motor Control ◽  
Eye Movements ◽  
Superior Colliculus ◽  
Motor Behavior ◽  
Saccadic Eye Movements ◽  
Population Coding ◽  
Population Activity ◽  
Low Levels

Population coding is a ubiquitous principle in the nervous system for the proper control of motor behavior. A significant amount of research is dedicated to studying population activity in the superior colliculus (SC) to investigate the motor control of saccadic eye movements. Vector summation with saturation (VSS) has been proposed as a mechanism for how population activity in the SC can be decoded to generate saccades. Interestingly, the model produces different predictions when decoding two simultaneous populations at high vs. low levels of activity. We tested these predictions by generating two simultaneous populations in the SC with high or low levels of dual microstimulation. We also combined varying levels of stimulation with visually induced activity. We found that our results did not perfectly conform to the predictions of the VSS scheme and conclude that the simplest implementation of the model is incomplete. We propose that additional parameters to the model might account for the results of this investigation.

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