A Model of Discovery: The Role of Imaging Established and Emerging Non-mammalian Models in Neuroscience

Abstract

Rodents have been the dominant animal models in neurobiology and neurological disease research over the past 60 years. The prevalent use of rats and mice in neuroscience research has been driven by several key attributes including their organ physiology being more similar to humans, the availability of a broad variety of behavioral tests and genetic tools, and widely accessible reagents. However, despite the many advances in understanding neurobiology that have been achieved using rodent models, there remain key limitations in the questions that can be addressed in these and other mammalian models. In particular, in vivo imaging in mammals at the cell-resolution level remains technically difficult and demands large investments in time and cost. The simpler nervous systems of many non-mammalian models allow for precise mapping of circuits and even the whole brain with impressive subcellular resolution. The types of non-mammalian neuroscience models available spans vertebrates and non-vertebrates, so that an appropriate model for most cell biological questions in neurodegenerative disease likely exists. A push to diversify the models used in neuroscience research could help address current gaps in knowledge, complement existing rodent-based bodies of work, and bring new insight into our understanding of human disease. Moreover, there are inherent aspects of many non-mammalian models such as lifespan and tissue transparency that can make them specifically advantageous for neuroscience studies. Crispr/Cas9 gene editing and decreased cost of genome sequencing combined with advances in optical microscopy enhances the utility of new animal models to address specific questions. This review seeks to synthesize current knowledge of established and emerging non-mammalian model organisms with advances in cellular-resolution in vivo imaging techniques to suggest new approaches to understand neurodegeneration and neurobiological processes. We will summarize current tools and in vivo imaging approaches at the single cell scale that could help lead to increased consideration of non-mammalian models in neuroscience research.

Addressing blood-brain-tumor-barrier heterogeneity in pediatric brain tumors with innovative preclinical models

“…The anatomy of zebrafish brains is comparable to that of mammalian brains, with significant homology in molecular signatures and structure of distinct brain regions ( 89 ). Notable differences however do exist in terms of size and organization of distinct brain regions ( 90 – 92 ). In terms of the BBB, live imaging of zebrafish vascular transgenic marker lines has been applied to establish that the BBB in zebrafish begins to form at three days post-fertilization (dpf) and is fully functional at 10 dpf ( 93 , 94 ).…”

Zebrafish Models of Rare Neurological Diseases like Spinocerebellar Ataxias (SCAs): Advantages and Limitations

“…Significant advancements have been made in brain imaging technologies, including 3D imaging techniques, which can be effectively utilized in modeling and studying spinocerebellar ataxias (SCAs) and other neurodegenerative diseases in zebrafish. While the human brain is incredibly complex, containing billions of neurons, the adult zebrafish brain, with approximately 10 million neurons [67], and the larval zebrafish brain, with between 80,000 and 100,000 neurons [68], provide a simpler model for imaging the nervous system and investigating neurological disorders, as their general brain organization and functions are largely conserved. The combination of behavioral assays with imaging holds immense potential for examining neurodegenerative diseases.…”

“…The combination of behavioral assays with imaging holds immense potential for examining neurodegenerative diseases. Researchers have utilized stabilized or partially stabilized larvae in conjunction with multiphoton and light-sheet fluorescence microscopy (LSFM) to capture images of genetically encoded calcium indicators (GECIs) in various behaviors, including opto-motor control, auditory and visual responses, olfaction, and prey-capture decisions [67]. Additionally, techniques that can monitor whole-brain neural activity in freely swimming larval zebrafish have been described recently [69].…”