scholarly journals A pentylenetetrazole-induced kindling zebrafish larval model for evoked recurrent seizures

2019 ◽  
Author(s):  
Sha Sun ◽  
Chenyanwen Zhu ◽  
Manxiu Ma ◽  
Bing Ni ◽  
Lin Chen ◽  
...  

AbstractBackgroundTransient pentylenetetrazol (PTZ) treatment on zebrafish larvae has been widely accepted a promising animal model for human epilepsy. However, this model is not ideal due to its acuteness and lack of recurrent seizures, which are the key feature of epilepsy in human disease. It is important to develop a more sensitive zebrafish model for epilepsy with well-controlled, predictable, recurrent seizures.New MethodThe new method includes an experimental setup and a treatment protocol. The setup tracks the locomotion activity of up to 48 larvae simultaneously, while a visual stimulus can be presented to each of the 48 animals individually. The protocol treated the larvae through a water bath in 5 mM PTZ while being stimulated with rotating grating stimuli for 1 hour/day from 5 to 7 days postfertilization.ResultsThe setup captured the locomotion activity of zebrafish larvae during visual stimulation. The new protocol generated recurrent responses after flashing lights 4 hours post PTZ treatment. The effects could be suppressed by the anti-epileptic drug valproic acid. The characteristics of the visual stimulus play a major role in this kindling model.Comparisons with Existing MethodsWe compared the proposed method with the transient PTZ model and confirmed that the flashing-light-evoked recurrent seizure is a new feature in addition to the transient changes.ConclusionsThe new method generated non-drug-triggered predictable recurrent seizures in response to intermittent photic stimulation in zebrafish larvae and may serve as a sensitive method for anti-epileptic drug screening or a new research protocol in epilepsy research.

1976 ◽  
Vol 43 (2) ◽  
pp. 487-493 ◽  
Author(s):  
Robert I. Bermant ◽  
Robert B. Welch

Subjects were exposed to a visual and to an auditory stimulus that differed spatially in laterality of origin. The subjects were observed for visual biasing of auditory localization (the momentary influence of a light on the spatially perceived location of a simultaneously presented sound) and for auditory aftereffect (a change in perceived location of a sound that persists over time and is measured after termination of the visual stimulus). A significant effect of visual stimulation on auditory localization was found only with the measure of bias. Bias was tested as a function of degree of visual-auditory separation (10/20/30°), eye position (straight-ahead/visual stimulus fixation), and position of visual stimulus relative to auditory stimulus (left/right). Only eye position proved statistically significant; straight-ahead eye position induced more bias than did fixation of the visual stimulus.


1999 ◽  
Vol 81 (2) ◽  
pp. 895-907 ◽  
Author(s):  
James A. Edwards ◽  
Hollis T. Cline

Light-induced calcium influx into retinal axons is regulated by presynaptic nicotinic acetylcholine receptor activity in vivo. Visual activity is thought to be a critical factor in controlling the development of central retinal projections. Neuronal activity increases cytosolic calcium, which was hypothesized to regulate process outgrowth in neurons. We performed an in vivo imaging study in the retinotectal system of albino Xenopus laevis tadpoles with the fluorescent calcium indicator calcium green 1 dextran (CaGD) to test the role of calcium in regulating axon arbor development. We find that visual stimulus to the retina increased CaGD fluorescence intensity in retinal ganglion cell (RGC) axon arbors within the optic tectum and that branch additions to retinotectal axon arbors correlated with a local rise in calcium in the parent branch. We find three types of responses to visual stimulus, which roughly correlate with theon, off, and sustained response types of RGC reported by physiological criteria. Imaging in bandscan mode indicated that patterns of calcium transients were nonuniform throughout the axons. We tested whether the increase in calcium in the retinotectal axons required synaptic activity in the retina; intraocular application of tetrodotoxin (10 μM) or nifedipine (1 and 10 μM) blocked the stimulus-induced increase in RGC axonal fluorescence. A second series of pharmacological investigations was designed to determine the mechanism of the calcium elevation in the axon terminals within the optic tectum. Injection of bis-( o-aminophenoxy)- N, N, N′, N′-tetraacetic acid-AM (BAPTA-AM) (20 mM) into the tectal ventricle reduced axonal calcium levels, supporting the idea that visual stimulation increases axonal calcium. Injection of BAPTA (20 mM) into the tectal ventricle to chelate extracellular calcium also attenuated the calcium response to visual stimulation, indicating that calcium enters the axon from the extracellular medium. Caffeine (10 mM) caused a large increase in axonal calcium, indicating that intracellular stores contribute to the calcium signal. Presynaptic nicotinic acetylcholine receptors (nAChRs) may play a role in axon arbor development and the formation of the topographic retinotectal projection. Injection of nicotine (10 μM) into the tectal ventricle significantly elevated RGC axonal calcium levels, whereas application of the nAChR antagonist αBTX (100 nM) reduced the stimulus-evoked rise in RGC calcium fluorescence. These data suggest that light stimulus to the retina increases calcium in the axon terminal arbors through a mechanism that includes influx through nAChRs and amplification by calcium-induced calcium release from intracellular calcium stores. Such a mechanism may contribute to developmental plasticity of the retinotectal system by influencing both axon arbor elaboration and the strength of synaptic transmission.


2019 ◽  
Author(s):  
Elif Somer ◽  
John Allen ◽  
Joseph Brooks ◽  
Vaughan Buttrill ◽  
Amir-Homayoun Javadi

AbstractBackgroundSensory perception can be modulated by the phase of neural oscillations, especially in the theta and alpha ranges. Oscillatory activity in the visual cortex can be entrained by transcranial alternating current stimulation (tACS) as well as periodic visual stimulation (i.e., flicker). Combined tACS and visual flicker stimulation modulates blood-oxygen-level-dependent (BOLD) responses and concurrent 4 Hz auditory click-trains and tACS modulates auditory perception in a phase-dependent way.ObjectiveIn the present study, we investigated if phase synchrony between concurrent tACS and periodic visual stimulation (i.e., flicker) can modulate performance on a visual matching task.MethodsParticipants completed a visual matching task on a flickering visual stimulus while receiving either in-phase (0 degree) or asynchronous (180, 90, or 270 degrees) tACS at alpha or theta frequency. Stimulation was applied over either occipital cortex or dorsolateral prefrontal cortex (DLPFC).ResultsVisual performance was significantly better during theta frequency tACS over the visual cortex when it was in-phase (0 degree) with visual stimulus flicker, compared to anti-phase (180 degree). This effect did not appear with alpha frequency flicker or with DLPFC stimulation. Furthermore, a control sham group showed no effect. There were no significant performance differences amongst the asynchronous (180, 90, and 270 degrees) phase conditions.ConclusionExtending previous studies on visual and auditory perception, our results support a crucial role of oscillatory phase in sensory perception and demonstrate a behaviourally relevant combination of visual flicker and tACS. The spatial and frequency specificity of our results have implications for research on the functional organisation of perception.


2012 ◽  
Vol 81 (1) ◽  
pp. 110-121 ◽  
Author(s):  
Elizabeth A. Harvie ◽  
Julie M. Green ◽  
Melody N. Neely ◽  
Anna Huttenlocher

Streptococcus iniaecauses systemic infection characterized by meningitis and sepsis. Here, we report a larval zebrafish model ofS. iniaeinfection. Injection of wild-typeS. iniaeinto the otic vesicle induced a lethal infection by 24 h postinfection. In contrast, anS. iniaemutant deficient in polysaccharide capsule (cpsAmutant) was not lethal, with greater than 90% survival at 24 h postinfection. Live imaging demonstrated that both neutrophils and macrophages were recruited to localized otic infection with mutant and wild-typeS. iniaeand were able to phagocytose bacteria. Depletion of neutrophils and macrophages impaired host survival following infection with wild-typeS. iniaeand thecpsAmutant, suggesting that leukocytes are critical for host survival in the presence of both the wild-type and mutant bacteria. However, zebrafish larvae with impaired neutrophil function but normal macrophage function had increased susceptibility to wild-type bacteria but not thecpsAmutant. Taking these findings together, we have developed a larval zebrafish model ofS. iniaeinfection and have found that although neutrophils are important for controlling infection with wild-typeS. iniae, neutrophils are not necessary for host defense against thecpsAmutant.


2018 ◽  
Vol 30 (2) ◽  
pp. 219-233 ◽  
Author(s):  
Masih Rahmati ◽  
Golbarg T. Saber ◽  
Clayton E. Curtis

Although the content of working memory (WM) can be decoded from the spatial patterns of brain activity in early visual cortex, how populations encode WM representations remains unclear. Here, we address this limitation by using a model-based approach that reconstructs the feature encoded by population activity measured with fMRI. Using this approach, we could successfully reconstruct the locations of memory-guided saccade goals based on the pattern of activity in visual cortex during a memory delay. We could reconstruct the saccade goal even when we dissociated the visual stimulus from the saccade goal using a memory-guided antisaccade procedure. By comparing the spatiotemporal population dynamics, we find that the representations in visual cortex are stable but can also evolve from a representation of a remembered visual stimulus to a prospective goal. Moreover, because the representation of the antisaccade goal cannot be the result of bottom–up visual stimulation, it must be evoked by top–down signals presumably originating from frontal and/or parietal cortex. Indeed, we find that trial-by-trial fluctuations in delay period activity in frontal and parietal cortex correlate with the precision with which our model reconstructed the maintained saccade goal based on the pattern of activity in visual cortex. Therefore, the population dynamics in visual cortex encode WM representations, and these representations can be sculpted by top–down signals from frontal and parietal cortex.


2009 ◽  
Vol 77 (9) ◽  
pp. 3651-3660 ◽  
Author(s):  
Jean-Pierre Levraud ◽  
Olivier Disson ◽  
Karima Kissa ◽  
Isabelle Bonne ◽  
Pascale Cossart ◽  
...  

ABSTRACT The zebrafish, Danio rerio, has become a popular vertebrate model for the study of infections, mainly because of its excellent optical accessibility at the embryonic and larval stages, when the innate immune system is already effective. We have thus tested the susceptibility of zebrafish larvae to the human pathogen Listeria monocytogenes, a gram-positive, facultative, intracellular bacterium that is known to survive and multiply in professional phagocytes and that causes fatal meningitis and abortions. Intravenous injection of early zebrafish larvae resulted in a progressive and ultimately fatal infection. Blood-borne L. monocytogenes bacteria were quickly trapped and engulfed by macrophages, an event that, for the first time, could be captured in vivo and in real time. Granulocytes also participated in the innate immune response. As in mammals, bacteria could escape the macrophage phagosome in a listeriolysin-dependent manner and accessed the cytosol; this event was critical for bacterial virulence, as listeriolysin-deficient bacteria were completely avirulent. Actin comet tails and protrusions were observed, suggesting cell-to-cell spread; these phenomena also played a role in virulence in zebrafish larvae, as actA-deficient bacteria were attenuated. These results demonstrate the relevance of the genetically tractable and optically accessible zebrafish model for the study of L. monocytogenes pathogenesis and particularly for the dissection of its interactions with phagocytes in vivo, a key factor of L. monocytogenes virulence.


Cephalalgia ◽  
2013 ◽  
Vol 33 (6) ◽  
pp. 365-374 ◽  
Author(s):  
Ritobrato Datta ◽  
Geoffrey K Aguirre ◽  
Siyuan Hu ◽  
John A Detre ◽  
Brett Cucchiara

Objective The objective of this study was to compare the interictal cortical response to a visual stimulus between migraine with aura (MWA), migraine without aura (MwoA), and control subjects. Methods In a prospective case-control study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to assess the response to a visual stimulus and arterial spin labeled perfusion MR to determine resting cerebral blood flow. A standardized questionnaire was used to assess interictal visual discomfort. Results Seventy-five subjects (25 MWA, 25 MwoA, and 25 controls) were studied. BOLD fMRI response to visual stimulation within primary visual cortex was greater in MWA (3.09 ± 0.15%) compared to MwoA (2.36 ± 0.13%, p = 0.0008) and control subjects (2.47 ± 0.11%, p = 0.002); responses were also greater in the lateral geniculate nuclei in MWA. No difference was found between MwoA and control groups. Whole brain analysis showed that increased activation in MWA was confined to the occipital pole. Regional resting cerebral blood flow did not differ between groups. MWA and MwoA subjects had significantly greater levels of interictal visual discomfort compared to controls ( p = 0.008 and p = 0.005, respectively), but this did not correlate with BOLD response. Conclusions Despite similar interictal symptoms of visual discomfort, only MWA subjects have cortical hyperresponsiveness to visual stimulus, suggesting a direct connection between cortical hyperresponsiveness and aura itself.


2019 ◽  
Author(s):  
Lihong Gong ◽  
Linyuan Yu ◽  
Xiaohong Gong ◽  
Cheng Wang ◽  
Naihua Hu ◽  
...  

Abstract Background: Inflammation is a general pathological phenomenon that operates during severe disturbance of homeostasis. Forsythiaside A (FA) and Forsythiaside B (FB) are isolated from air-dried fruits of Forsythia suspensa, which show a significant effect against inflammation. However, the anti-inflammatory effect and therapeutic mechanism have not yet been clarified in zebrafish. Methods: In this study, the anti-inflammatory effects of FA and FB were investigated in CuSO4-induced zebrafish model. Intracellular ROS and NO generation in zebrafish were performed using fluorescent probe dyes. Metabolomics and proteomics using liquid chromatography mass spectrometry were carried out to identify the expression of metabolites and proteins associated with chemically induced inflammation in zebrafish larvae. Quantitative PCR was performed to detect the progressive changes in the genes.Results: FA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO4-induced ROS and NO generation in zebrafish. Metabolomics analyses indicated that the Nicotinate and nicotinamide metabolism, Amino sugar and nucleotide sugar metabolism, Pyrimidine metabolism and Purine metabolism were mainly involved. The proteomic analyses identified 146 differentially expressed proteins, among which, the expression of collagen (col2a1b, col9a2, col9a1b), nme3, wdr3, mrps7, srpx, gch2, ptpn11a, rcvrn2, nit2, scaf4a and zgc:162509 were all reversed both in FA and FB groups. FA and FB could reverse the abnormal expression of these metabolites and proteins to alleviate chemical damage to the neuromasts in the lateral line of zebrafish.Conclusions: FA and FB possess remarkable anti-inflammatory effect and could be used to protect chemically induced neuromasts damage in zebrafish larvae.


2017 ◽  
Author(s):  
Amra Covic ◽  
Christian Keitel ◽  
Emanuele Porcu ◽  
Erich Schröger ◽  
Matthias M Müller

ABSTRACTThe neural processing of a visual stimulus can be facilitated by attending to its position or by a co-occurring auditory tone. Using frequency-tagging we investigated whether facilitation by spatial attention and audio-visual synchrony rely on similar neural processes. Participants attended to one of two flickering Gabor patches (14.17 and 17 Hz) located in opposite lower visual fields. Gabor patches further “pulsed” (i.e. showed smooth spatial frequency variations) at distinct rates (3.14 and 3.63 Hz). Frequency-modulating an auditory stimulus at the pulse-rate of one of the visual stimuli established audio-visual synchrony. Flicker and pulsed stimulation elicited stimulus-locked rhythmic electrophysiological brain responses that allowed tracking the neural processing of simultaneously presented stimuli. These steady-state responses (SSRs) were quantified in the spectral domain to examine visual stimulus processing under conditions of synchronous vs. asynchronous tone presentation and when respective stimulus positions were attended vs. unattended. Strikingly, unique patterns of effects on pulse- and flicker driven SSRs indicated that spatial attention and audiovisual synchrony facilitated early visual processing in parallel and via different cortical processes. We found attention effects to resemble the classical top-down gain effect facilitating both, flicker and pulse-driven SSRs. Audio-visual synchrony, in turn, only amplified synchrony-producing stimulus aspects (i.e. pulse-driven SSRs) possibly highlighting the role of temporally co-occurring sights and sounds in bottom-up multisensory integration.


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