Department of Molecular and Cellular Biology, Harvard University
HCBI: Center for Biological Imaging, Harvard University
Neural circuits and behavior in larval zebrafish
The general goal of the laboratory is the comprehensive identification and examination of neural circuits controlling behavior using the larval zebrafish as a model system. To that end, we have established and quantified a series of visually induced behaviors and analyzed the individual resulting motor components. Using these assays in combination with various calcium indicators and two-photon microscopy we have monitored neuronal activity throughout the fish brain in an awake and intact preparation. An extended goal is the study of how changes or variations in the behavior are reflected in changes in the underlying neuronal activity. To that end, we have developed several quantitative learning assays and tools for in vivo monitoring of neural activity in freely swimming larvae.
Neuroscientists have long been working to understand how biological structures can produce the complex behaviors that are generated by the nervous system. However, even the basic operational principles governing a brain’s interconnected network of cells have remained painfully elusive. My laboratory is working on a scientific strategy focused on building a complete, multi-level picture of simple neural circuits that will advance our basic understanding of brain function and offers a complete view into the neuronal activity underlying a series of relatively complex behaviors.
Generally the question of how the brain, or neural circuits in particular, function ought to be reduced to the question of what the brain or particular parts of the brain are doing. This is best addresses by rigorous and quantitative behavioral assays that allow us to relate a particular set of input stimuli – in our case visual signals that get translated by the retina into action potentials in ganglion cells – to a set of motor actions that are controlled by an array of spikes in motor neurons – the output of the system. Both data-sets can be assessed to a first order by behavioral experiments. The second question then has to be how the neurons and synapses within the circuit actually perform this computation. Important insights into this problem can be gained by recording activity in every neuron of the fish’s brain in the context of a specific behavior. This would be a truly daunting task in any mammalian preparation but the small and transparent brain of the larval zebrafish allowed us to develop and extend the technology that makes it possible to acquire these datasets in fish expressing genetically encoded indicators in all neurons1. In parallel we have tried to simplify the question by the examination of individual modules in the brain. Here, we have started to make progress by finding specific nuclei in the fish brain - the optic tectum which processes inputs directly from the retina2 on the one hand and the reticular spinal formation, a set of identified neurons that exclusively controls behavior3,4, on the other hand - that provide stepping stones on the long journey to a complete understanding of the brain and its role in producing behavior.
Dunn, T.W., Mu, Y., Narayan, S., Randlett, O., Naumann, E.A., Yang, C.T., Schier, A.F., Freeman, J., Engert, F., and Ahrens, M.B. Brain-wide mapping of neural activity controlling zebrafish exploratory locomotion. Elife. (5) -. 2016.
Dunn, T.W., Gebhardt C., Naumann E.A., Riegler C., Ahrens M.B., Engert F., Del Bene F. Neural Circuits Underlying Visually Evoked Escapes in Larval Zebrafish. Neuron 89 (3):613-628, 2016.
Randlett O., Wee C.L., Naumann E.A., Nnaemeka O., Schoppik D., Fitzgerald J.E., Portugues R., Lacoste A.M., Riegler C., Engert F., Schier A.F. Whole-brain activity mapping onto a zebrafish brain atlas. Nature Methods 12 (11):1039-1046, 2015.
Severi, K. E., Portugues, R., Marques, J. C., O'Malley, D. M., Orger, M. B. and Engert, F. Neural control and modulation of swimming speed in the larval zebrafish. Neuron 83 (3):692-707, 2014.
Portugues, R., Feierstein, C. E., Engert, F., and Orger, M. B. Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior. Neuron (81) 1328-1343. 2014.
Ahrens MB, Li JM, Orger MB, Robson DN, Schier AF, Engert F and Portugues R. (2012) Brain-wide neural dynamics at single-cell resolution during rapid motor adaptation in larval zebrafish. Nature 485(7399):471-7.
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