A virtual reality system to analyze neural activity and behavior in adult zebrafish

Virtual realities are powerful tools to analyze and manipulate interactions between animals and their environment and to enable measurements of neuronal activity during behavior. In many species, however, optical access to the brain and/or the behavioral repertoire are limited. We developed a high-resolution virtual reality for head-restrained adult zebrafish, which exhibit cognitive behaviors not shown by larvae. We noninvasively measured activity throughout the dorsal telencephalon by multiphoton calcium imaging. Fish in the virtual reality showed regular swimming patterns and were attracted to animations of conspecifics. Manipulations of visuo-motor feedback revealed neurons that responded selectively to the mismatch between the expected and the actual visual consequences of motor output. Such error signals were prominent in multiple telencephalic areas, consistent with models of predictive processing. A virtual reality system for adult zebrafish therefore provides opportunities to analyze neuronal processing mechanisms underlying higher brain functions including decision making, associative learning, and social interactions. Complex behaviors and the underlying neural activity in adult zebrafish can be accessed through a virtual reality system in combination with two-photon microscopy.

[1]  V. Jayaraman,et al.  Ring attractor dynamics in the Drosophila central brain , 2017, Science.

[2]  D. Wolpert,et al.  Central cancellation of self-produced tickle sensation , 1998, Nature Neuroscience.

[3]  Michael H. Dickinson,et al.  A modular display system for insect behavioral neuroscience , 2008, Journal of Neuroscience Methods.

[4]  Herwig Baier,et al.  Biological Motion as an Innate Perceptual Mechanism Driving Social Affiliation , 2018, Current Biology.

[5]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[6]  Georg B. Keller,et al.  Predictive Processing: A Canonical Cortical Computation , 2018, Neuron.

[7]  Germán Sumbre,et al.  Fast functional imaging of multiple brain regions in intact zebrafish larvae using Selective Plane Illumination Microscopy , 2013, BMC Neuroscience.

[8]  E. Yaksi,et al.  Identification of a neuronal population in the telencephalon essential for fear conditioning in zebrafish , 2018, BMC Biology.

[9]  Rainer W Friedrich,et al.  High-resolution optical control of spatiotemporal neuronal activity patterns in zebrafish using a digital micromirror device , 2012, Nature Protocols.

[10]  Drew N. Robson,et al.  Brain-wide neuronal dynamics during motor adaptation in zebrafish , 2012, Nature.

[11]  Cristina Broglio,et al.  Conservation of Spatial Memory Function in the Pallial Forebrain of Reptiles and Ray-Finned Fishes , 2002, The Journal of Neuroscience.

[12]  D. Tank,et al.  Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice , 2007, Neuron.

[13]  Michael B. Reiser,et al.  Corrigendum: Two-photon calcium imaging from head-fixed Drosophila during optomotor walking behavior , 2011, Nature Methods.

[14]  F. Del Bene,et al.  Transparent Danionella translucida as a genetically tractable vertebrate brain model , 2018, Nature Methods.

[15]  Dal Hyung Kim,et al.  Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish , 2017, Nature Methods.

[16]  Tobias Bonhoeffer,et al.  Two-photon calcium imaging in mice navigating a virtual reality environment. , 2014, Journal of visualized experiments : JoVE.

[17]  Kenneth D. Harris,et al.  Community-based benchmarking improves spike rate inference from two-photon calcium imaging data , 2018, PLoS Comput. Biol..

[18]  Rainer W Friedrich,et al.  Associative conditioning remaps odor representations and modifies inhibition in a higher olfactory brain area , 2019, Nature Neuroscience.

[19]  A. Wanner,et al.  Dense EM-based reconstruction of the interglomerular projectome in the zebrafish olfactory bulb , 2016, Nature Neuroscience.

[20]  Robert Gerlai,et al.  Shoaling develops with age in Zebrafish (Danio rerio) , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[21]  Gonçalo Lopes,et al.  Development of social behavior in young zebrafish , 2015, Front. Neural Circuits.

[22]  Nadine S. J. Lysiak,et al.  Kin recognition and inbreeding avoidance in zebrafish, Danio rerio, is based on phenotype matching , 2006, Animal Behaviour.

[23]  A Schnee,et al.  Rats are able to navigate in virtual environments , 2005, Journal of Experimental Biology.

[24]  J. Eisen,et al.  Forebrain Control of Behaviorally Driven Social Orienting in Zebrafish , 2018, Current Biology.

[25]  Alexander Attinger,et al.  Visuomotor Coupling Shapes the Functional Development of Mouse Visual Cortex , 2017, Cell.

[26]  R. Portugues,et al.  Ontogeny of classical and operant learning behaviors in zebrafish. , 2012, Learning & memory.

[27]  Robert Gerlai,et al.  Animated images in the analysis of zebrafish behavior , 2016, Current zoology.

[28]  C. Harvey,et al.  Neuroscience: Virtual reality explored , 2016, Nature.

[29]  R. Saxe,et al.  Theory of Mind: A Neural Prediction Problem , 2013, Neuron.

[30]  Rainer W Friedrich,et al.  Remote z-scanning with a macroscopic voice coil motor for fast 3D multiphoton laser scanning microscopy , 2016, Biomedical optics express.

[31]  Michael B. Reiser,et al.  Real neuroscience in virtual worlds , 2012, Current Opinion in Neurobiology.

[32]  Junichi Nakai,et al.  Real-Time Visualization of Neuronal Activity during Perception , 2013, Current Biology.

[33]  Ruben Portugues,et al.  Optogenetics in a transparent animal: circuit function in the larval zebrafish , 2013, Current Opinion in Neurobiology.

[34]  Melissa Hardy,et al.  The Tol2kit: A multisite gateway‐based construction kit for Tol2 transposon transgenesis constructs , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[35]  Timothy W. Dunn,et al.  Spinal Projection Neurons Control Turning Behaviors in Zebrafish , 2013, Current Biology.

[36]  Hitoshi Okamoto,et al.  Imaging of Neural Ensemble for the Retrieval of a Learned Behavioral Program , 2013, Neuron.

[37]  Christel Genoud,et al.  Analyzing the structure and function of neuronal circuits in zebrafish , 2013, Front. Neural Circuits.

[38]  D. Tank,et al.  Intracellular dynamics of hippocampal place cells during virtual navigation , 2009, Nature.

[39]  Donald M. O’Malley,et al.  Prey Tracking by Larval Zebrafish: Axial Kinematics and Visual Control , 2005, Brain, Behavior and Evolution.

[40]  Sam E Benezra,et al.  Supplemental Information Population-level Representation of a Temporal Sequence Underlying Song Production in the Zebra Finch , 2022 .

[41]  Rainer W. Friedrich,et al.  Circuit Neuroscience in Zebrafish , 2010, Current Biology.

[42]  Mark J Schnitzer,et al.  Three-Photon Imaging of Mouse Brain Structure and Function through the Intact Skull , 2018, Nature Methods.

[43]  Georg B. Keller,et al.  Sensorimotor Mismatch Signals in Primary Visual Cortex of the Behaving Mouse , 2012, Neuron.

[44]  Delbert Dueck,et al.  Clustering by Passing Messages Between Data Points , 2007, Science.

[45]  Iain D. Couzin,et al.  Virtual Reality for Freely Moving Animals , 2017, Nature Methods.

[46]  Masahiko Hibi,et al.  Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish , 2008, Proceedings of the National Academy of Sciences.

[47]  M. Wullimann,et al.  Optimized Gal4 genetics for permanent gene expression mapping in zebrafish , 2009, Proceedings of the National Academy of Sciences.

[48]  Su Guo,et al.  The dorsal pallium in zebrafish, Danio rerio (Cyprinidae, Teleostei) , 2011, Brain Research.

[49]  Philipp J. Keller,et al.  Whole-brain functional imaging at cellular resolution using light-sheet microscopy , 2013, Nature Methods.

[50]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[51]  Nathan C. Klapoetke,et al.  A High-Light Sensitivity Optical Neural Silencer: Development and Application to Optogenetic Control of Non-Human Primate Cortex , 2010, Front. Syst. Neurosci..

[52]  Karl J. Friston,et al.  Canonical Microcircuits for Predictive Coding , 2012, Neuron.

[53]  Akihiro Urasaki,et al.  Olfactory neural circuitry for attraction to amino acids revealed by transposon-mediated gene trap approach in zebrafish , 2009, Proceedings of the National Academy of Sciences.

[54]  A. Borst.  Seeing smells: imaging olfactory learning in bees , 1999, Nature Neuroscience.

[55]  Na Ji.  Adaptive optical fluorescence microscopy , 2017, Nature Methods.

[56]  Karel Svoboda,et al.  ScanImage: Flexible software for operating laser scanning microscopes , 2003, Biomedical engineering online.

[57]  M. Dickinson,et al.  Active flight increases the gain of visual motion processing in Drosophila , 2010, Nature Neuroscience.

[58]  K. Cullen.  Vestibular processing during natural self-motion: implications for perception and action , 2019, Nature Reviews Neuroscience.

[59]  W. Denk,et al.  Imaging in vivo: watching the brain in action , 2008, Nature Reviews Neuroscience.