Model Organisms in Translational Neuroscience: From Neural Circuits and Behaviour to Clinical Insight.

Model organisms have transformed our understanding of the nervous system. Drosophila melanogaster, Caenorhabditis elegans, Danio rerio (zebrafish), and Xenopus tadpoles offer conserved neurological architectures combined with rapid development, genetic accessibility, and experimental scale that are impractical in mammalian systems. These properties make them uniquely powerful tools for dissecting the cellular and molecular mechanisms of neural circuits, behaviour, and disease - and, increasingly, for accelerating the translation of fundamental discovery into clinical insight. Mechanisms identified in invertebrate and lower-vertebrate models have already informed our understanding of Alzheimer’s, Parkinson’s, ALS, neurodevelopmental disorders, and inherited neuropathies, and have provided platforms for high-throughput drug screening and target validation.Despite this progress, key questions remain. How faithfully do disease phenotypes in simple organisms recapitulate the molecular and circuit-level pathology of human conditions? Which mechanisms identified in these models translate to mammalian systems - and which do not? How can advances in genetic manipulation, functional imaging, single-cell omics, and AI-assisted analysis be combined with model organisms to accelerate the discovery of therapeutic targets and biomarkers? Addressing these questions is central to closing the gap between fundamental neurobiology and clinical innovation.This Research Topic invites submissions that leverage simple vertebrate and invertebrate animal models to dissect mechanisms of neurological and neurodevelopmental disorders and to evaluate strategies with translational potential. We welcome Original Research, Brief Research Reports, Methods, Reviews, Mini-Reviews, Perspectives, and Opinions addressing - but not limited to - the following themes:o Disease-relevant neural circuits and behaviour in model systems, including circuit dysfunction and translatable behavioural phenotypeso Mechanisms of neurodegeneration, neuroprotection, and neural repair, and their implications for therapeutic strategyo Model organisms in neurological and neurodevelopmental disease research, including the identification of novel therapeutic targetso Cross-species translation of conserved disease mechanisms from invertebrates and lower vertebrates to mammalian systemso Genetic, genomic, and optogenetic approaches to therapeutic target discovery and pathway validationo Neuropharmacology, drug discovery, and target validation using model organism platformso Functional imaging, connectomics, and behavioural phenotyping applied to disease modelso Gene-environment interactions in nervous system disease, with relevance to preventive or therapeutic interventionso Translational neuroscience approaches that bridge fundamental discovery and clinical innovationo Emerging technologies - AI-assisted analysis, single-cell and spatial omics, advanced microscopy, and next-generation genetic tools - applied to disease-relevant questions in model organismso Rigor, reproducibility, and responsible use of model organisms in translational research - experimental design, reporting standards (e.g., ARRIVE), the 3Rs, and emerging ethical considerations in preclinical model organism studies that inform human therapeutics.Together, these contributions will highlight how the experimental power of model organisms can be harnessed to advance the diagnosis, treatment, and prevention of neurological disease. Topic editors: Stella Koutsikou, Fani Papagiannouli Source: https://www.frontiersin.org/research-topics/83112/model-organisms-in-translational-neuroscience-from-neural-circuits-and-behaviour-to-clinical-insight