Microfluidics for Investigation of Electric-Induced Behaviors of Zebrafish Larvae
Notice bibliographique
Résumé
Zebrafish has emerged as a model organism for studying the genetic, neuronal and behavioral bases of diseases and for drug screening. Being a vertebrate, they are phylogenetically closer to humans than invertebrates, possess complex organs and the overall organization of their brain shows structural similarities with human. They are small at larval stages, optically transparent and easy to culture. In addition, zebrafish models of human diseases and genetic mutants are widely available. These characteristics make this vertebrate model an ideal organism for neurodegeneration study and drug screening from the molecule to whole organism level. Despite these attractive features, the conventional zebrafish screening methods used for movement-based behavioral tests are mostly time-consuming, uncontrollable, qualitative, low-throughput and inaccurate. Zebrafish larvae behavioral response to various stimulations including optical and chemical stimuli, have been already investigated. However, zebrafish sensory-motor responses to electrical signals, a controllable stimulus which its potential in inducing locomotion response was proven in research done before, have not been broadly studied. Examples of research questions remaining to be answered are if zebrafish electric induced response is sensitive to different electric current intensities, voltage drops, multiple electrical stimulation, and the electric field direction. The involvement of different pathways and genes in this response and its potential for utilization in disease studies and chemical screening, and drug discovery can also be investigated. This research aims to enhance our understanding of zebrafish electric-induced response via presenting novel microfluidic devices that address the challenges associated with monitoring the behavioral activities of zebrafish larvae in response to various electrical signals. In Objective 1 of the thesis, we designed a microfluidic device to deliver electrical stimuli to the awake and partially immobilized zebrafish larvae, screen and study their phenotypic behavioral responses and analyze the outputs. Behavioral response was characterized in terms of response duration and tail beat frequency. A multi-phenotypic microfluidic device was also developed to study the effect of electric stimulation on the heartrate. In Objective 2, attention was given to investigate the effect of electric current, voltage, and field direction on the zebrafish larvae’s response to find an optimized setting which can induce a traceable response in zebrafish. Using different habituation-dishabituation strategies, we also investigated if the zebrafish larvae show adaptation towards repeated exposures to electric stimuli. In Objective 3, we developed a quadruple-fish device to enhance the behavioral throughput of our microfluidic platform and showed the technique's effectiveness for larger sample size and faster behavioral assay. In Objective 4, our quadruple-fish device was employed to investigate the involvement of dopaminergic neurons in electric-induced movement response of zebrafish larvae. Lastly, since we could monitor the electric-induced behavioral responses of zebrafish larvae, in Objective 5, the applicability of our proposed technique in chemical toxicity and gene screening assays was investigated. \nThis study is expected to introduce a microfluidic platform for on-demand and phenotypic behavioral screening of zebrafish larvae with applications in chemical screening and drug discovery.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».