Imaging Approaches to Investigate Pathophysiological Mechanisms of Brain Disease in Zebrafish

Abstract

Zebrafish has become an essential model organism in modern biomedical research. Owing to its distinctive features and high grade of genomic homology with humans, it is increasingly employed to model diverse neurological disorders, both through genetic and pharmacological intervention. The use of this vertebrate model has recently enhanced research efforts, both in the optical technology and in the bioengineering fields, aiming at developing novel tools for high spatiotemporal resolution imaging. Indeed, the ever-increasing use of imaging methods, often combined with fluorescent reporters or tags, enable a unique chance for translational neuroscience research at different levels, ranging from behavior (whole-organism) to functional aspects (whole-brain) and down to structural features (cellular and subcellular). In this work, we present a review of the imaging approaches employed to investigate pathophysiological mechanisms underlying functional, structural, and behavioral alterations of human neurological diseases modeled in zebrafish.

Acousto-optic deflectors in experimental neuroscience: overview of theory and applications

“…A central quest in neuroscience is to unveil complex neuronal dynamics and understand their correlation to pathological conditions in vertebrate organisms [1][2][3][4][5][6] to clarify equivalent human neural mechanisms [7,8]. In this framework, advanced light microscopy represents the tool of choice [9,10] to non-invasively image extended neuronal populations [11,12] at both cellular and subcellular scales [13].…”

Two-photon all-optical electrophysiology for the dissection of larval zebrafish brain functional connectivity

“…In this framework, the ever-increasing use of the tiny and translucent zebrafish larva as an animal model 11 , has provided momentum for the development and enhancement of optical technologies aimed at imaging and controlling neuronal activity with light at high spatio-temporal resolution 12-14 . On the imaging side, previous high-resolution all-optical investigations on zebrafish have made use of two-photon (2P) point scanning methods 15-17 or, more rarely, of one-photon (1P) excitation light-sheet fluorescence microscopy (LSFM) 18 .…”

“…Over the last few decades, with the advent of optogenetics 5 and the widespread adoption of genetically encoded fluorescent indicators 6 , all-optical methods have gained traction for their ability to simultaneously monitor and manipulate the activity of multiple neurons within the intact brain [7][8][9][10] . In this framework, the ever-increasing use of the tiny and translucent zebrafish larva as an animal model 11 , has provided momentum for the development and enhancement of optical technologies aimed at imaging and controlling neuronal activity with light at high spatio-temporal resolution [12][13][14] . On the imaging side, previous high-resolution all-optical investigations on zebrafish have made use of two-photon (2P) point scanning methods [15][16][17] or, more rarely, of one-photon (1P) excitation lightsheet fluorescence microscopy (LSFM) 18 .…”

A single-cell transcriptomic atlas reveals resident dendritic-like cells in the zebrafish brain parenchyma

“…In contrast, the CNS immune cell repertoire of other vertebrate models is poorly defined. This is the case for the zebrafish, an increasingly recognized model for translational research on human neurological diseases, owing to its strong genetics and conserved physiology with mammals (Turrini et al 2023;Liu 2023;D'Amora et al 2023). Over the years, the zebrafish has also gained considerable importance in regenerative research due to its remarkable capacities for organ regeneration, including the CNS.…”