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      Larval zebrafish as a model for studying individual variability in translational neuroscience research

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          Abstract

          The larval zebrafish is a popular model for translational research into neurological and psychiatric disorders due to its conserved vertebrate brain structures, ease of genetic and experimental manipulation and small size and scalability to large numbers. The possibility of obtaining in vivo whole-brain cellular resolution neural data is contributing important advances into our understanding of neural circuit function and their relation to behavior. Here we argue that the larval zebrafish is ideally poised to push our understanding of how neural circuit function relates to behavior to the next level by including considerations of individual differences. Understanding variability across individuals is particularly relevant for tackling the variable presentations that neuropsychiatric conditions frequently show, and it is equally elemental if we are to achieve personalized medicine in the future. We provide a blueprint for investigating variability by covering examples from humans and other model organisms as well as existing examples from larval zebrafish. We highlight recent studies where variability may be hiding in plain sight and suggest how future studies can take advantage of existing paradigms for further exploring individual variability. We conclude with an outlook on how the field can harness the unique strengths of the zebrafish model to advance this important impending translational question.

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          Most cited references62

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          Similar network activity from disparate circuit parameters.

          It is often assumed that cellular and synaptic properties need to be regulated to specific values to allow a neuronal network to function properly. To determine how tightly neuronal properties and synaptic strengths need to be tuned to produce a given network output, we simulated more than 20 million versions of a three-cell model of the pyloric network of the crustacean stomatogastric ganglion using different combinations of synapse strengths and neuron properties. We found that virtually indistinguishable network activity can arise from widely disparate sets of underlying mechanisms, suggesting that there could be considerable animal-to-animal variability in many of the parameters that control network activity, and that many different combinations of synaptic strengths and intrinsic membrane properties can be consistent with appropriate network performance.
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            The brain basis of language processing: from structure to function.

            Language processing is a trait of human species. The knowledge about its neurobiological basis has been increased considerably over the past decades. Different brain regions in the left and right hemisphere have been identified to support particular language functions. Networks involving the temporal cortex and the inferior frontal cortex with a clear left lateralization were shown to support syntactic processes, whereas less lateralized temporo-frontal networks subserve semantic processes. These networks have been substantiated both by functional as well as by structural connectivity data. Electrophysiological measures indicate that within these networks syntactic processes of local structure building precede the assignment of grammatical and semantic relations in a sentence. Suprasegmental prosodic information overtly available in the acoustic language input is processed predominantly in a temporo-frontal network in the right hemisphere associated with a clear electrophysiological marker. Studies with patients suffering from lesions in the corpus callosum reveal that the posterior portion of this structure plays a crucial role in the interaction of syntactic and prosodic information during language processing.
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              Genetically encoded indicators of neuronal activity.

              Experimental efforts to understand how the brain represents, stores and processes information require high-fidelity recordings of multiple different forms of neural activity within functional circuits. Thus, creating improved technologies for large-scale recordings of neural activity in the live brain is a crucial goal in neuroscience. Over the past two decades, the combination of optical microscopy and genetically encoded fluorescent indicators has become a widespread means of recording neural activity in nonmammalian and mammalian nervous systems, transforming brain research in the process. In this review, we describe and assess different classes of fluorescent protein indicators of neural activity. We first discuss general considerations in optical imaging and then present salient characteristics of representative indicators. Our focus is on how indicator characteristics relate to their use in living animals and on likely areas of future progress.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                23 June 2023
                2023
                : 17
                : 1143391
                Affiliations
                [1] 1Institute of Human Genetics, University Medical Center of Johannes Gutenberg University Mainz , Mainz, Germany
                [2] 2Living Systems Institute, Faculty of Health and Life Sciences, University of Exeter , Exeter, United Kingdom
                Author notes

                Edited by: Marco Lorenzo Dal Maschio, University of Padua, Italy

                Reviewed by: Eric Horstick, West Virginia University, United States; Suresh Jesuthasan, Nanyang Technological University, Singapore

                *Correspondence: Soojin Ryu, s.ryu@ 123456exeter.ac.uk
                Article
                10.3389/fnbeh.2023.1143391
                10328419
                37424749
                da5aa274-bc47-46ff-9363-4012d105f715
                Copyright © 2023 Jacobs and Ryu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 January 2023
                : 22 May 2023
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 62, Pages: 7, Words: 6190
                Funding
                Funded by: Bundesministerium für Bildung und Forschung, doi 10.13039/501100002347;
                The writing of this manuscript was funded by the Dennis and Mireille Gillings Foundation and the German Federal Office for Education and Research (BMBF) Grant Number 01GQ1404 to SR.
                Categories
                Neuroscience
                Mini Review
                Custom metadata
                Individual and Social Behaviors

                Neurosciences
                zebrafish,individual variability,translational neuroscience,neural circuit,in vivo imaging

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