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Review
. 2024 Mar 12:17:1358844.
doi: 10.3389/fnmol.2024.1358844. eCollection 2024.

Diving into the zebrafish brain: exploring neuroscience frontiers with genetic tools, imaging techniques, and behavioral insights

Affiliations
Review

Diving into the zebrafish brain: exploring neuroscience frontiers with genetic tools, imaging techniques, and behavioral insights

O Doszyn et al. Front Mol Neurosci. .

Abstract

The zebrafish (Danio rerio) is increasingly used in neuroscience research. Zebrafish are relatively easy to maintain, and their high fecundity makes them suitable for high-throughput experiments. Their small, transparent embryos and larvae allow for easy microscopic imaging of the developing brain. Zebrafish also share a high degree of genetic similarity with humans, and are amenable to genetic manipulation techniques, such as gene knockdown, knockout, or knock-in, which allows researchers to study the role of specific genes relevant to human brain development, function, and disease. Zebrafish can also serve as a model for behavioral studies, including locomotion, learning, and social interactions. In this review, we present state-of-the-art methods to study the brain function in zebrafish, including genetic tools for labeling single neurons and neuronal circuits, live imaging of neural activity, synaptic dynamics and protein interactions in the zebrafish brain, optogenetic manipulation, and the use of virtual reality technology for behavioral testing. We highlight the potential of zebrafish for neuroscience research, especially regarding brain development, neuronal circuits, and genetic-based disorders and discuss its certain limitations as a model.

Keywords: behavioral studies; brain development; brain imaging; genetic tools; modern methods for neuroscience; optogenetics; virtual reality; zebrafish.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Number of publications per year using zebrafish since year 2000 (from Pubmed database). (B) Comparison of relative numbers of publications per year using zebrafish and mouse models showing dynamic growth of the zebrafish research.
FIGURE 2
FIGURE 2
(A) Schematic visualization and exemplary image of the use of the Gal4-UAS system. (B) Schematic visualization and exemplary image of the use of the Tol2 system. (C) Schematic visualization and exemplary image of the use of the Cre-loxP system. (D) Schematic visualization and exemplary image of the use of the Tet-ON system.
FIGURE 3
FIGURE 3
(A) Schematic visualization and exemplary image of the use of photoconvertible and photoactivatable proteins. (B) Schematic visualization of the use of the laser ablation method. (C) Example of the use of the laser ablation method in zebrafish brain research.
FIGURE 4
FIGURE 4
(A) Schematic visualization of the use of the FingRs. (B) FingR-PSD95 binds endogenous PSD-95 protein at the postsynaptic density.
FIGURE 5
FIGURE 5
Trans-Tango method for live trans-synaptic tracing in zebrafish (details in the main text).
FIGURE 6
FIGURE 6
(A) Schematic visualization of the FRET principle. (B) Exemplary image of neurons in the zebrafish brain showing FRET.
FIGURE 7
FIGURE 7
(A) Schematic representation of the use of channelrhodopsins to activate neuronal circuits with light-off (A) and light-on conditions (A’). B. Schematic representation of the use of anion channelrhodopsins to inactivate neuronal circuits with light-off (B) and light-on conditions (B’).

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