Background: Since 2004, zebrafish have become the state-of-the-art, in vivo model for biomedical research due to their genetic and physiological homology with humans, inexpensive high-quantity breeding, and quick development in a highly-controlled environment suitable for longitudinal studies. New Method: To fully utilize the zebrafish model, a novel, automated, high-throughput system was designed. Shoals of five zebrafish were placed in 16 tanks and automatically fed over two days for a total of 16 training sessions. Color LED lights were used as the stimulus for each shoal coinciding with the release of food for a duration of 20 seconds. This system was tested on two age groups: 6- and 11-month-old. Results: After three training sessions, the median height of the school in the tank during stimulus was significantly higher than that of the na ï ve fish during the first training session. All subsequent training sessions demonstrated similar behaviour. A decline in memory retention, as defined by a reduction in the median height during light stimulus ( i.e. no simultaneous food delivery), was observed 8 days post training. Comparison with existing methods: The high-throughput nature of this system allows for simultaneous training of 16 tanks of fish under identical conditions without human interaction and provides a means to rapidly assess their learning and memory behaviours. Conclusion: Results provide a baseline for understanding the normal cognitive processes of learning and memory retention in zebrafish. This work paves the way for future studies on the impacts of therapeutic agents on these cognitive processes.
Jones, L.J., McCutcheon, J.E., Young, A.M.J. and Norton, W.H.J. (2015) Neurochemical Measurements in the Zebrafish Brain. Frontiers in Behavioral Neuroscience, 9, 1-16. https://doi.org/10.3389/fnbeh.2015.00246
Gerlai, R., Chatterjee, D., Pereira, T., Sawashima, T. and Krishnannair, R. (2009) Acute and Chronic Alcohol Dose: Population Differences in Behavior and Neurochemistry of Zebrafish. Genes, Brain and Behavior, 8, 586-599. https://doi.org/10.1111/j.1601-183X.2009.00488.x
Kalueff, A.V., Echevarria, D.J. and Stewart, A.M. (2014) Gaining Translational Momentum: More Zebrafish Models for Neuroscience Research. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 55, 1-6. https://doi.org/10.1016/j.pnpbp.2014.01.022
Sison, M. and Gerlai, R. (2011) Associative Learning Performance Is Impaired in Zebrafish (Danio rerio) by the NMDA-R Antagonist MK-801. Neurobiology of Learning and Memory, 96, 230-237. https://doi.org/10.1016/j.nlm.2011.04.016
McMenamin, S., Chandless, M. and Parichy, D.M. (2016) Working with Zebrafish at Postembryonic Stages. Methods in Cell Biology, 134, 587-607. https://doi.org/10.1016/bs.mcb.2015.12.001
Stewart, A.M., Braubach, O., Spitsbergen, J., Gerlai, R. and Kalueff, A.V. (2014) Zebrafish Models for Translational Neuroscience Research: From Tank to Bedside. Trends Neurosci., 37, 264-278. https://doi.org/10.1016/j.tins.2014.02.011
Valentim, A.M., Félix, L.M., Carvalho, L., Diniz, E. and Antunes, L.M. (2016) A New Anaesthetic Protocol for Adult Zebrafish (Danio rerio): Propofol Combined with Lidocaine. PLoS One, 11, 1-12. https://doi.org/10.1371/journal.pone.0147747
Barbazuk, W.B., Korf, I., Kadavi, C., et al. (2000) The Synthenic Relationship of the Zebrafish and Human Genomes. Genome Research, 10, 1351-1358. https://doi.org/10.1101/gr.144700
Panula, P., Sallinen, V., Sundvik, M., et al. (2006) Modulatory Neurotransmitter Systems and Behavior: Towards Zebrafish Models of Neurodegenerative Diseases. Zebrafish, 3, 235-247. https://doi.org/10.1089/zeb.2006.3.235
Saif, M., Chatterjee, D., Buske, C. and Gerlai, R. (2013) Sight of Conspecific Images Induces Changes in Neurochemistry in Zebrafish. Behavioural Brain Research, 243, 294-299. https://doi.org/10.1016/j.bbr.2013.01.020
Bandmann, O. and Burton, E.A. (2010) Genetic Zebrafish Models of Neurodegenerative Diseases. Neurobiology of Disease, 40, 58-65. https://doi.org/10.1016/j.nbd.2010.05.017
Lieschke, G.J. and Currie, P.D. (2007) Animal Models of Human Disease: Zebrafish Swim into View. Nature Reviews Genetics, 8, 353-367. https://doi.org/10.1038/nrg2091
Sun, Z. (2004) A Genetic Screen in Zebrafish Identifies Cilia Genes as a Principal Cause of Cystic Kidney. Development, 131, 4085-4093. https://doi.org/10.1242/dev.01240
Jerman, S. and Sun, Z. (2017) Using Zebrafish to Study Kidney Development and Disease. Current Topics in Developmental Biology, 124, 41-79. https://doi.org/10.1016/bs.ctdb.2016.11.008
Wilkins, B.J. and Pack, M. (2013) Zebrafish Models of Human Liver Development and Disease. Comprehensive Physiology, 3, 1213-1230. https://doi.org/10.1002/cphy.c120021
Miller, N., Greene, K., Dydinski, A. and Gerlai, R. (2013) Effects of Nicotine and Alcohol on Zebrafish (Danio rerio) Shoaling. Behavioural Brain Research, 240, 192-196. https://doi.org/10.1016/j.bbr.2012.11.033
Parker, M.O., Millington, M.E., Combe, F.J. and Brennan, C.H. (2012) Housing Conditions Differentially Affect Physiological and Behavioural Stress Responses of Zebrafish, as well as the Response to Anxiolytics. PLoS ONE, 7, e34992.
Gerlai, R., Lee, V. and Blaser, R. (2006) Effects of Acute and Chronic Ethanol Exposure on the Behavior of Adult Zebrafish (Danio rerio). Pharmacology Biochemistry and Behavior, 85, 752-761. https://doi.org/10.1016/j.pbb.2006.11.010
Miklósi, A. and Andews, R.J. (2006) The Zebrafish as a Model for Behavioral Studies. Zebrafish, 3, 227-234. https://doi.org/10.1089/zeb.2006.3.227
Biggers, J.D., Finn, C.A. and McLaren, A. (1962) Long-Term Reproductive Performance of Female Mice II. Variation of Litter Size with Parity. Journal of Reproduction and Fertility, 3, 313-330.
Fernandes, Y.M., Rampersad, M., Luchiari, A.C. and Gerlai, R. (2016) Associative Learning in the Multichamber Tank: A New Learning Paradigm for Zebrafish. Behavioural Brain Research, 312, 279-284. https://doi.org/10.1016/j.bbr.2016.06.038
Gómez-Laplaza, L.M. and Gerlai, R. (2010) Latent Learning in Zebrafish (Danio rerio). Behavioural Brain Research, 208, 509-515. https://doi.org/10.1016/j.bbr.2009.12.031
Blaser, R.E. and Vira, D.G. (2014) Experiments on Learning in Zebrafish (Danio rerio), A Promising Model of Neurocognitive Function. Neuroscience & Biobehavioral Reviews, 42, 224-231. https://doi.org/10.1016/j.neubiorev.2014.03.003
Kalueff, A.V., Stewart, A.M., Gerlai, R. and Court, P. (2015) Zebrafish as an Emerging Model for Studying Complex Brain Disorders. Trends in Pharmacological Sciences, 35, 63-75. https://doi.org/10.1016/j.tips.2013.12.002
Johnson, T.E. and Hutchinson, E.W. (1993) Absence of Strong Heterosis for Life Span and Other Life History Traits in Caenorhabditis elegans. Genetics, 134, 465-474.
Al-Imari, L. and Gerlai, R. (2008) Sight of Conspecifics as Reward in Associative Learning in Zebrafish (Danio rerio). Behavioural Brain Research, 189, 216-219. https://doi.org/10.1016/j.bbr.2007.12.007
Wolman, M.A., Jain, R.A., Liss, L. and Granato, M. (2011) Chemical Modulation of Memory Formation in Larval Zebrafish. Proceedings of the National Academy of Sciences of the United States of America, 108, 15468-15473. https://doi.org/10.1073/pnas.1107156108
Hinz, F.I., Aizenberg, M., Tushev, G. and Schuman, E.M. (2013) Protein Synthesis-Dependent Associative Long-Term Memory in Larval Zebrafish. Journal of Neuroscience, 33, 15382-15387. https://doi.org/10.1523/JNEUROSCI.0560-13.2013
Blank, M., Guerim, L.D., Cordeiro, R.F. and Vianna, M.R.M. (2009) A One-Trial Inhibitory Avoidance Task to Zebrafish: Rapid Acquisition of an NMDA-Dependent Long-Term Memory. Neurobiology of Learning and Memory, 92, 529-534. https://doi.org/10.1016/j.nlm.2009.07.001
Braubach, O.R., Wood, H.D., Gadbois, S., Fine, A. and Croll, R.P. (2009) Olfactory Conditioning in the Zebrafish (Danio rerio). Behavioural Brain Research, 198, 190-198. https://doi.org/10.1016/j.bbr.2008.10.044
Mathur, P., Lau, B. and Guo, S. (2011) Conditioned Place Preference Behavior in Zebrafish. Nature Protocols, 6, 338-345. https://doi.org/10.1038/nprot.2010.201
Del Bene, F., Wyart, C., Robles, E., et al. (2011) Filtering of Visual Information in the Tectum by an Identified Neural Circuit. Science, 330, 669-673. https://doi.org/10.1126/science.1192949
Wyart, C., Del Bene, F., Warp, E., et al. (2009) Optogenetic Dissection of a Behavioural Module in the Vertebrate Spinal Cord. Nature, 461, 407-410. https://doi.org/10.1038/nature08323
Fetcho, J.R. and McLean, D.L. (2010) Some Principles of Organization of Spinal Neurons Underlying Locomotion in Zebrafish and Their Implications. Annals of the New York Academy of Sciences, 1198, 94-104. https://doi.org/10.1111/j.1749-6632.2010.05539.x
Valente, A., Huang, K.-H., Portugues, R. and Engert, F. (2012) Ontogeny of Classical and Operant Learning Behaviors in Zebrafish. Learning & Memory, 19, 170-177. https://doi.org/10.1101/lm.025668.112
Spence, R., Gerlach, G., Lawrence, C. and Smith, C. (2008) The Behaviour and Ecology of the Zebrafish Danio rerio. Biological Reviews, 83, 13-34. https://doi.org/10.1111/j.1469-185X.2007.00030.x
Gleason, P.E., Weber, P.G. and Weber, S.P. (1977) Effect of Group Size on Avoidance Learning in Zebra Fish, Brachy Danio rerio (Pisces: Cyprinidae). Animal Learning & Behavior, 5, 213-216. https://doi.org/10.3758/BF03214081
Vital, C. and Martins, E.P. (2013) Socially-Central Zebrafish Influence Group Behavior More than Those on the Social Periphery. PLoS ONE, 8, e55503. https://doi.org/10.1371/journal.pone.0055503
Griffin, G. (2012) Evaluating Environmental Enrichment Is Essential. Enrichment Record, 29-33.
Kistler, C., Hegglin, D., Würbel, H. and Konig, B. (2011) Preference for Structured Environment in Zebrafish (Danio rerio) and Checker Barbs (Puntius oligolepis). Applied Animal Behaviour Science, 135, 318-327. https://doi.org/10.1016/j.applanim.2011.10.014
Reed, B. and Jennings, M. (2011) Guidance on the Housing and Care of Zebrafish Danio rerio. Res. Anim. Dep. Sci. Group, RSPCA, 1-27.
Yeh, C.M., Glock, M. and Ryu, S. (2013) An Optimized Whole-Body Cortisol Quantification Method for Assessing Stress Levels in Larval Zebrafish. PLoS ONE, 8, e79406. https://doi.org/10.1371/journal.pone.0079406
Pavlidis, M., Digka, N., Theodoridi, A., et al. (2013) Husbandry of Zebrafish, Danio rerio, and the Cortisol Stress Response. Zebrafish, 10, 524-531. https://doi.org/10.1089/zeb.2012.0819
Ramsay, J.M., Fiest, G.W., Varga, Z.M., Westerfield, M., Kent, M.A. and Schreck, C.B. (2015) Whole-Body Cortisol Response of Zebrafish to Acute Net Handling Stress. Aquaculture, 297, 157-162. https://doi.org/10.1016/j.aquaculture.2009.08.035
Southwell, M., Galassi, M. and McRobert, S. (2012) Fish Cam: An Online Tool for Introducing Shoaling Behavior to the Classroom. Zebrafish, 9, 242-245. https://doi.org/10.1089/zeb.2012.0755
Doyle, J.M., Merovitch, N., Wyeth, R.C., et al. (2017) A Simple Automated System for Appetitive Conditioning of Zebrafish in Their Home Tanks. Behavioural Brain Research, 317, 444-452. https://doi.org/10.1016/j.bbr.2016.09.044
Wyeth, R.C., Braubach, O.R., Fine, A. and Croll, R.P. (2010) Videograms: A Method for Repeatable Unbiased Quantitative Behavioral Analysis without Scoring or Tracking CO. Neuromethods, 51, 15-33.
Suriyampola, P.S., Sykes, D.J., Khemka, A., Shelton, D.S., Bhat, A. and Martins, E.P. (2016) Water Flow Impacts Group Behavior in Zebrafish (Danio rerio). Behavioral Ecology, 1-7.
Care CC on A (1993) Guide to the Care and Use of Experimental Animals. Vol. 1, 2nd Edition, Canadian Council on Animal Care, Ottawa.
Branson, K., Robie, A., Bender, J., Perona, P. and Dickinson, M. (2009) High-Throughput Ethomics in Large Groups of Drosophila. Nature Methods, 6, 451-457. https://doi.org/10.1038/nmeth.1328
Taborsky, M. (2010) Sample Size in the Study of Behaviour. Ethology, 116, 185-202. https://doi.org/10.1111/j.1439-0310.2010.01751.x
SmartTots. Funding Anesthesia Research to Ensure Pediatric Safety. http://smarttots.org/
The Effect of General Anesthesia on the Developing Brain: Appreciating Parent Concerns while Allaying Their Fears. http://www.apsf.org/newsletters/html/2016/Oct/04_DevBrain.htm