scholarly journals Long term visuo-vestibular mismatch in freely behaving mice differentially affects gaze stabilizing reflexes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Filipa França de Barros ◽  
Louise Schenberg ◽  
Michele Tagliabue ◽  
Mathieu Beraneck
Keyword(s):  
Time Course ◽  
Head Movements ◽  
Visual Signals ◽  
High Contrast ◽  
Similar Time ◽  
Optokinetic Reflex ◽  
Vestibulo Ocular Reflex ◽  
Freely Behaving ◽  
Frequency Selective ◽  
Recovery Dynamics

AbstractThe vestibulo-ocular reflex (VOR) and the optokinetic reflex (OKR) work synergistically to stabilize gaze in response to head movements. We previously demonstrated that a 14-day visuo-vestibular mismatch (VVM) protocol applied in freely behaving mice decreased the VOR gain. Here, we show for the first time that the OKR gain is also reduced and report on the recovery dynamics of both VOR and OKR after the end of the VVM protocol. Using sinusoidally-modulated stimulations, the decreases in VOR and OKR were found to be frequency-selective with larger reductions for frequencies < 0.5 Hz. Constant-velocity OKR stimulation tests demonstrated that the persistent components of the OKR were not modified while the transient, initial responses were. To identify the signals driving VOR and OKR reductions, we compared the responses of mice exposed to a high-contrast and no-contrast VVM. Despite being more robust in the high-contrast conditions, reductions were largely comparable and recovered with a similar time course. An analysis that directly compared VOR and OKR responses revealed that, alterations in the VOR were of significantly larger amplitude with significantly slower dynamics of recovery. Our findings are evidence for a frequency-selective influence of visual signals in the tuning of gaze stabilizing reflexes in normal mice.

Eye-Head Movement Coordination: Vestibulo-Ocular Reflex Suppression with Head-Fixed Target Fixation1

1991 ◽  
Vol 1 (2) ◽  
pp. 161-170
Author(s):  
Jean-Louis Vercher ◽  
Gabriel M. Gauthier
Keyword(s):  
Eye Movements ◽  
Time Course ◽  
Mental Arithmetic ◽  
Visual Space ◽  
Head Movements ◽  
Total Darkness ◽  
Fixed Target ◽  
Ocular Reflex ◽  
Optokinetic Reflex ◽  
Vestibulo Ocular Reflex

To maintain clear vision, the images on the retina must remain reasonably stable. Head movements are generally dealt with successfully by counter-rotation of the eyes induced by the combined actions of the vestibulo-ocular reflex (VOR) and the optokinetic reflex. A problem of importance relates to the value of the so-called intrinsic gain of the VOR (VORG) in man, and how this gain is modulated to provide appropriate eye movements. We have studied these problems in two situations: 1. fixation of a stationary object of the visual space while the head moves; 2. fixation of an object moving with the head. These two situations were compared to a basic condition in which no visual target was allowed in order to induce “pure” VOR. Eye movements were recorded in seated subjects during stationary sinusoidal and transient rotations around the vertical axis. Subjects were in total darkness (DARK condition) and involved in mental arithmetic. Alternatively, they were provided with a small foveal target, either fixed with respect to earth (earth-fixed target: EFT condition), or moving with them (chair-fixed-target: CFT condition). The stationary rotation experiment was used as baseline for the ensuing experiment and yielded control data in agreement with the literature. In all 3 visual conditions, typical responses to transient rotations were rigorously identical during the first 200 ms. They showed, sequentially, a 16-ms delay of the eye behind the head and a rapid increase in eye velocity during 75 to 80 ms, after which the average VORG was 0.9 ± 0.15. During the following 50 to 100 ms, the gain remained around 0.9 in all three conditions. Beyond 200 ms, the VORG remained around 0.9 in DARK and increased slowly towards 1 or decreased towards zero in the EFT and CFT conditions, respectively. The time-course of the later events suggests that visual tracking mechanisms came into play to reduce retinal slip through smooth pursuit, and position error through saccades. Our data also show that in total darkness VORG is set to 0.9 in man. Lower values reported in the literature essentially reflect predictive properties of the vestibulo-ocular mechanism, particularly evident when the input signal is a sinewave.

scholarly journals Changes in neural activity around the time of saccades: Separate contributions of visual and non-visual signals on MEG alpha and theta band activity

2021 ◽  
Author(s):  
David Acunzo ◽  
David Melcher
Keyword(s):  
Neural Activity ◽  
Visual Processing ◽  
Time Course ◽  
Brain Regions ◽  
Visual Input ◽  
Visual Signals ◽  
Perceptual Task ◽  
Alpha Power ◽  
Similar Time ◽  
Retinal Stimulation

Visual processing mainly occurs during fixation, periods separated by saccadic eye movements, necessitating a close coordination between sensory and motor systems. It has been suggested that the intention to make a saccade can modulate neural activity, including predictive changes, suppression of peri-saccadic retinal input and trans-saccadic integration. Consistent with this idea, modulations of neural activity around the time of saccades have been reported in non-human species, showing non-visually mediated, extraretinal responses in specific brain regions. In humans, however, peri-saccadic whole-brain activity has mainly been studied in the context of a perceptual task, making it difficult to disentangle activity related to the task, visual transients from retinal stimulation and non-visual (saccade-related) responses. We measured magnetoencephalography (MEG) theta (3–7 Hz) and alpha (8–12 Hz) activity during voluntary horizontal saccade execution between two fixation points. To distinguish between visually and non-visually mediated activity, participants engaged in three tasks: voluntary saccades in near-darkness, fixation with visual input shifted to simulate the saccade, and volitional saccades in total darkness. Using correlational analyses, we found that patterns of neural activity are consistent with contributions of two separate mechanisms, one related to saccades (non-visual/extraretinal) and the other linked to the processing of visual input at the beginning of the new fixation (visual/retinal). Changes in occipital alpha power and instantaneous frequency showed a similar time course in near-dark and simulated saccade conditions, suggesting an effect of visually evoked responses. In contrast, alterations in parietal-occipital theta power and phase clustering were consistent with a non-visually-driven (extraretinal) mechanism, with similar multivariate patterns for near-dark and full-darkness conditions. Some effects, such as theta phase reset and alterations in alpha power, showed separable contributions of both the saccade and visual transient, with differing time courses. This combination of visual and non-visual mechanisms may support sensorimotor integration during active vision.

scholarly journals Human vestibulo-ocular reflex adaptation is frequency selective

2019 ◽  
Vol 122 (3) ◽  
pp. 984-993 ◽  
Author(s):  
Carlo N. Rinaudo ◽  
Michael C. Schubert ◽  
William V. C. Figtree ◽  
Christopher J. Todd ◽  
Americo A. Migliaccio
Keyword(s):  
High Frequency ◽  
Head Rotation ◽  
Head Movements ◽  
Head Impulse ◽  
Ocular Reflex ◽  
Before And After ◽  
Vestibulo Ocular Reflex ◽  
Vor Adaptation ◽  
Frequency Selective ◽  
Head Rotations

The vestibulo-ocular reflex (VOR) is the only system that maintains stable vision during rapid head rotations. The VOR gain (eye/head velocity) can be trained to increase using a vestibular-visual mismatch stimulus. We sought to determine whether low-frequency (sinusoidal) head rotation during training leads to changes in the VOR during high-frequency head rotation testing, where the VOR is more physiologically relevant. We tested eight normal subjects over three sessions. For training protocol 1, subjects performed active sinusoidal head rotations at 1.3 Hz while tracking a laser target, whose velocity incrementally increased relative to head velocity so that the VOR gain required to stabilize the target went from 1.1 to 2 over 15 min. Protocol 2 was the same as protocol 1, except that head rotations were at 0.5 Hz. For protocol 3, head rotation frequency incrementally increased from 0.5 to 2 Hz over 15 min, while the VOR gain required to stabilize the target was kept at 2. We measured the active and passive, sinusoidal (1.3Hz) and head impulse VOR gains before and after each protocol. Sinusoidal and head impulse VOR gains increased in protocols 1 and 3; however, although the sinusoidal VOR gain increase was ~20%, the related head impulse gain increase was only ~10%. Protocol 2 resulted in no-gain adaptation. These data show human VOR adaptation is frequency selective, suggesting that if one seeks to increase the higher-frequency VOR response, i.e., where it is physiologically most relevant, then higher-frequency head movements are required during training, e.g., head impulses. NEW & NOTEWORTHY This study shows that human vestibulo-ocular reflex adaptation is frequency selective at frequencies >0.3 Hz. The VOR in response to mid- (1.3 Hz) and high-frequency (impulse) head rotations were measured before and after mid-frequency sinusoidal VOR adaptation training, revealing that the mid-frequency gain change was higher than high-frequency gain change. Thus, if one seeks to increase the higher-frequency VOR response, where it is physiologically most relevant, then higher-frequency head movements are required during training.

scholarly journals Loss of α-9 Nicotinic Acetylcholine Receptor Subunit Predominantly Results in Impaired Postural Stability Rather Than Gaze Stability

2022 ◽  
Vol 15 ◽  
Author(s):  
Hui Ho Vanessa Chang ◽  
Barbara J. Morley ◽  
Kathleen E. Cullen
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Microelectromechanical Systems ◽  
Vestibular Function ◽  
Head Movements ◽  
Wild Type ◽  
Nicotinic Acetylcholine ◽  
Optokinetic Reflex ◽  
Gaze Stability ◽  
Vestibulo Ocular Reflex

The functional role of the mammalian efferent vestibular system (EVS) is not fully understood. One proposal is that the mammalian EVS plays a role in the long-term calibration of central vestibular pathways, for example during development. Here to test this possibility, we studied vestibular function in mice lacking a functional α9 subunit of the nicotinic acetylcholine receptor (nAChR) gene family, which mediates efferent activation of the vestibular periphery. We focused on an α9 (−/−) model with a deletion in exons 1 and 2. First, we quantified gaze stability by testing vestibulo-ocular reflex (VOR, 0.2–3 Hz) responses of both α9 (−/−) mouse models in dark and light conditions. VOR gains and phases were comparable for both α9 (−/−) mutants and wild-type controls. Second, we confirmed the lack of an effect from the α9 (−/−) mutation on central visuo-motor pathways/eye movement pathways via analyses of the optokinetic reflex (OKR) and quick phases of the VOR. We found no differences between α9 (−/−) mutants and wild-type controls. Third and finally, we investigated postural abilities during instrumented rotarod and balance beam tasks. Head movements were quantified using a 6D microelectromechanical systems (MEMS) module fixed to the mouse’s head. Compared to wild-type controls, we found head movements were strikingly altered in α9 (−/−) mice, most notably in the pitch axis. We confirmed these later results in another α9 (−/−) model, with a deletion in the exon 4 region. Overall, we conclude that the absence of the α9 subunit of nAChRs predominately results in an impairment of posture rather than gaze.

Postnatal growth rate and gonadal development in circadian tau mutant hamsters reared in constant dim red light

Reproduction ◽  
2000 ◽  
pp. 327-330 ◽  
Author(s):  
RJ Lucas ◽  
JA Stirland ◽  
YN Mohammad ◽  
AS Loudon
Keyword(s):  
Time Course ◽  
Red Light ◽  
Somatic Growth ◽  
Postnatal Growth ◽  
Gonadal Development ◽  
Testicular Development ◽  
Wild Type ◽  
Similar Time ◽  
Syrian Hamsters ◽  
Body Weights

The role of the circadian clock in the reproductive development of Syrian hamsters (Mesocricetus auratus was examined in wild type and circadian tau mutant hamsters reared from birth to 26 weeks of age under constant dim red light. Testis diameter and body weights were determined at weekly intervals in male hamsters from 4 weeks of age. In both genotypes, testicular development, subsequent regression and recrudescence exhibited a similar time course. The age at which animals displayed reproductive photosensitivity, as exhibited by testicular regression, was unrelated to circadian genotype (mean +/- SEM: 54 +/- 3 days for wild type and 59 +/- 5 days for tau mutants). In contrast, our studies revealed a significant impact of the mutation on somatic growth, such that tau mutants weighed 18% less than wild types at the end of the experiment. Our study reveals that the juvenile onset of reproductive photoperiodism in Syrian hamsters is not timed by the circadian system.

scholarly journals Neurofilament Proteolysis after Focal Ischemia; When Do Cells Die after Experimental Stroke?

1999 ◽  
Vol 19 (6) ◽  
pp. 652-660 ◽  
Author(s):  
Jaroslaw Aronowski ◽  
Ki-Hyun Cho ◽  
Roger Strong ◽  
James C. Grotta
Keyword(s):  
Time Course ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Cellular Damage ◽  
Experimental Stroke ◽  
Infarct Core ◽  
Similar Time ◽  
The Core ◽  
Tetrazolium Staining ◽  
Previous Demonstration

To determine the occurrence and time-course of presumably irreversible subcellular damage after moderate focal ischemia, rats were subjected to 1, 3, 6, 9, or 24 hours of permanent unilateral middle cerebral and common carotid occlusion or 3 hours of reversible occlusion followed by 3, 6, or 21 hours of reperfusion. The topography and the extent of damage were analyzed with tetrazolium staining and immunoblot using an antibody capable of detecting breakdown of neurofilament. Neurofilament proteolysis began after 3 hours in the infarct core but was still incomplete in penumbral regions up to 9 hours. Similarly, tetrazolium-staining abnormalities were observed in the core of 50% of animals after 3 hours of ischemia. At 6 hours of permanent ischemia, infarct volume was maximal, and further prolongation of occlusion to 9 or 24 hours did not increase abnormal tetrazolium staining. In contrast to permanent ischemia and in agreement with the authors' previous demonstration of “reperfusion injury” in this model, prolongation of reperfusion from 3 hours to 6 and 21 hours after 3 hours of reversible occlusion gradually augmented infarct volume by 203% and 324%, respectively. Neurofilament proteolysis initiated approximately 3 hours after ischemia was quantitatively greatest in the core and extended during reperfusion to incorporate penumbra with a similar time course to that of tetrazolium abnormalities. These data demonstrate that, at least as measured by neurofilament breakdown and mitochondrial failure, extensive cellular damage is not present in penumbral regions for up to 9 hours, suggesting the potential for rescuing these regions by appropriate and timely neuroprotective strategies.

scholarly journals TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei

2021 ◽  
Author(s):  
Carolin Schilpp ◽  
Robin Lochbaum ◽  
Peter Braubach ◽  
Danny Jonigk ◽  
Manfred Frick ◽  
...  
Keyword(s):  
Time Course ◽  
Atopic Asthma ◽  
Ciliated Cells ◽  
Cell Nuclei ◽  
Tissue Remodelling ◽  
Similar Time ◽  
Airway Epithelia ◽  
Epithelial Integrity ◽  
Motile Cilia ◽  
Tgf Β1

AbstractTGF-β1 is a major mediator of airway tissue remodelling during atopic asthma and affects tight junctions (TJs) of airway epithelia. However, its impact on TJs of ciliated epithelia is sparsely investigated. Herein we elaborated effects of TGF-β1 on TJs of primary human bronchial epithelial cells. We demonstrate that TGF-β1 activates TGF-β1 receptors TGFBR1 and TGFBR2 resulting in ALK5-mediated phosphorylation of SMAD2. We observed that TGFBR1 and -R2 localize specifically on motile cilia. TGF-β1 activated accumulation of phosphorylated SMAD2 (pSMAD2-C) at centrioles of motile cilia and at cell nuclei. This triggered an increase in paracellular permeability via cellular redistribution of claudin 3 (CLDN3) from TJs into cell nuclei followed by disruption of epithelial integrity and formation of epithelial lesions. Only ciliated cells express TGF-β1 receptors; however, nuclear accumulations of pSMAD2-C and CLDN3 redistribution were observed with similar time course in ciliated and non-ciliated cells. In summary, we demonstrate a role of motile cilia in TGF-β1 sensing and showed that TGF-β1 disturbs TJ permeability of conductive airway epithelia by redistributing CLDN3 from TJs into cell nuclei. We conclude that the observed effects contribute to loss of epithelial integrity during atopic asthma.

scholarly journals Pseudo-streaming potentials in Necturus gallbladder epithelium. II. The mechanism is a junctional diffusion potential.

1992 ◽  
Vol 99 (3) ◽  
pp. 317-338 ◽  
Author(s):  
L Reuss ◽  
B Simon ◽  
C U Cotton
Keyword(s):  
Time Course ◽  
Bathing Solution ◽  
Intercellular Spaces ◽  
Similar Time ◽  
Streaming Potentials ◽  
Osmotic Water ◽  
Lateral Intercellular Spaces ◽  
Transepithelial Voltage ◽  
Time Courses ◽  
Good Agreement

The mechanisms of apparent streaming potentials elicited across Necturus gallbladder epithelium by addition or removal of sucrose from the apical bathing solution were studied by assessing the time courses of: (a) the change in transepithelial voltage (Vms). (b) the change in osmolality at the cell surface (estimated with a tetrabutylammonium [TBA+]-selective microelectrode, using TBA+ as a tracer for sucrose), and (c) the change in cell impermeant solute concentration ([TMA+]i, measured with an intracellular double-barrel TMA(+)-selective microelectrode after loading the cells with TMA+ by transient permeabilization with nystatin). For both sucrose addition and removal, the time courses of Vms were the same as the time courses of the voltage signals produced by [TMA+]i, while the time courses of the voltage signals produced by [TBA+]o were much faster. These results suggest that the apparent streaming potentials are caused by changes of [NaCl] in the lateral intercellular spaces, whose time course reflects the changes in cell water volume (and osmolality) elicited by the alterations in apical solution osmolality. Changes in cell osmolality are slow relative to those of the apical solution osmolality, whereas lateral space osmolality follows cell osmolality rapidly, due to the large surface area of lateral membranes and the small volume of the spaces. Analysis of a simple mathematical model of the epithelium yields an apical membrane Lp in good agreement with previous measurements and suggests that elevations of the apical solution osmolality elicit rapid reductions in junctional ionic selectivity, also in good agreement with experimental determinations. Elevations in apical solution [NaCl] cause biphasic transepithelial voltage changes: a rapid negative Vms change of similar time course to that of a Na+/TBA+ bi-ionic potential and a slow positive Vms change of similar time course to that of the sucrose-induced apparent streaming potential. We conclude that the Vms changes elicited by addition of impermeant solute to the apical bathing solution are pseudo-streaming potentials, i.e., junctional diffusion potentials caused by salt concentration changes in the lateral intercellular spaces secondary to osmotic water flow from the cells to the apical bathing solution and from the lateral intercellular spaces to the cells. Our results do not support the notion of junctional solute-solvent coupling during transepithelial osmotic water flow.

scholarly journals Correlation between Charge Movement and Ionic Current during Slow Inactivation in Shaker K+ Channels

1997 ◽  
Vol 110 (5) ◽  
pp. 579-589 ◽  
Author(s):  
Riccardo Olcese ◽  
Ramón Latorre ◽  
Ligia Toro ◽  
Francisco Bezanilla ◽  
Enrico Stefani
Keyword(s):  
Time Course ◽  
Voltage Dependence ◽  
Ionic Current ◽  
K Channel ◽  
Charge Movement ◽  
Slow Inactivation ◽  
Gating Currents ◽  
Similar Time ◽  
K Channels ◽  
Recovery From Inactivation

Prolonged depolarization induces a slow inactivation process in some K+ channels. We have studied ionic and gating currents during long depolarizations in the mutant Shaker H4-Δ(6–46) K+ channel and in the nonconducting mutant (Shaker H4-Δ(6–46)-W434F). These channels lack the amino terminus that confers the fast (N-type) inactivation (Hoshi, T., W.N. Zagotta, and R.W. Aldrich. 1991. Neuron. 7:547–556). Channels were expressed in oocytes and currents were measured with the cut-open-oocyte and patch-clamp techniques. In both clones, the curves describing the voltage dependence of the charge movement were shifted toward more negative potentials when the holding potential was maintained at depolarized potentials. The evidences that this new voltage dependence of the charge movement in the depolarized condition is associated with the process of slow inactivation are the following: (a) the installation of both the slow inactivation of the ionic current and the inactivation of the charge in response to a sustained 1-min depolarization to 0 mV followed the same time course; and (b) the recovery from inactivation of both ionic and gating currents (induced by repolarizations to −90 mV after a 1-min inactivating pulse at 0 mV) also followed a similar time course. Although prolonged depolarizations induce inactivation of the majority of the channels, a small fraction remains non–slow inactivated. The voltage dependence of this fraction of channels remained unaltered, suggesting that their activation pathway was unmodified by prolonged depolarization. The data could be fitted to a sequential model for Shaker K+ channels (Bezanilla, F., E. Perozo, and E. Stefani. 1994. Biophys. J. 66:1011–1021), with the addition of a series of parallel nonconducting (inactivated) states that become populated during prolonged depolarization. The data suggest that prolonged depolarization modifies the conformation of the voltage sensor and that this change can be associated with the process of slow inactivation.

scholarly journals Calcium metabolism in rat hepatocytes

1978 ◽  
Vol 170 (3) ◽  
pp. 615-625 ◽  
Author(s):  
S Foden ◽  
P J Randle
Keyword(s):  
Cyclic Amp ◽  
Time Course ◽  
Rat Hepatocytes ◽  
Ionophore A23187 ◽  
Total Calcium ◽  
Free Medium ◽  
Adrenergic Agonists ◽  
Calcium Efflux ◽  
Similar Time ◽  
Carbonyl Cyanide

1. The total calcium concentration in rat hepatocytes was 7.9 microgram-atoms/g dry wt.; 77% of this was mitochondrial. Approx. 20% of cell calcium exchanged with 45Ca within 2 min. Thereafter incorporation proceeded at a low rate to reach 28% of total calcium after 60 min. Incorporation into mitochondria showed a similar time course and accounted for 20% of mitochondrial total calcium after 60 min. 2. The alpha-adrenergic agonists phenylephrine and adrenaline + propranolol stimulated incorporation of 45Ca into hepatocytes. Phenylephrine was shown to increase total calcium in hepatocytes. Phenylephrine inhibited efflux fo 45Ca from hepatocytes perifused with calcium-free medium. 3. Glucagon, dibutryl cyclic AMP and beta-adrenergic agonists adrenaline and 3-isobutyl-1-methyl-xanthine stimulated calcium efflux from hepatocytes perifused with calcium-free medium. The effect of glucagon was blocked by insulin. Insulin itself had no effect on calcium efflux and it did not affect the response to dibutyryl cyclic AMP. 4. Incorporation of 45Ca into mitochondria in hepatocytes was stimulated by phenylephrine and inhibited by glucagon and by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. The effect of glucagon was blocked by insulin. 5. Ionophore A23187 stimulated hepatocyte uptake of 45Ca, uptake of 45Ca into mitochondria in hepatocytes and efflux of 45Ca into a calcium-free medium.

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