Neural circuits and behaviour

Our approach

In the Scott Lab, we are interested in the workings of the brain at the level of cells and circuits.  We aim to understand how sensory stimuli are perceived and processed in the brain, and how the brain then interprets these stimuli to produce adaptive behaviours.

Because of the brain’s extraordinary complexity, these questions are difficult to address by looking at individual cells.  The flow of information through the brain relies on the coordinated activity of thousands or millions of cells, and on ensembles of neurons that are active simultaneously.  For this reason, our research involves imaging activity in thousands of cells, and seeking salient patterns of activity across these populations.  In a range of projects, we characterise the neurons and circuits that respond to various visual, auditory, water flow, and vestibular stimuli; that play a role in the integration of information from these modalities; and that filter sensory information to produce behaviour.

We work in the zebrafish model system because of its strengths in genetics, behaviour, microscopy, and optogenetics.  Specifically, we use transgenic techniques to express genetically encoded calcium indicators (GECIs) or optogenetic proteins in specific parts of the zebrafish brain.  We then use selective plane illumination microscopy (SPIM) to observe the GECIs, which reveal activity across our cells and circuits.  We also use optical physics to produce holograms in the brain for optogenetics in our larval fish. Gradually, we aim to transition from describing patterns of activity in the brain to manipulating them in targeted ways, and to describing the structures and connectivity of the neurons carrying the information.  This will contribute to a comprehensive understanding of brain function spanning cells, circuits, regions, and the brain as a whole. A detailed review of these approaches can be found here.

Vision

From a broad perspective, this work is part of a burgeoning field of circuits neuroscience. Over the coming decades, neuroscientists will make the leap from understanding how regions of the brain function to describing, in concrete terms, the cellular circuits that underlie perception and behaviour.  Our group hopes to contribute to this effort, specifically in describing how the senses work, how the brain produces a coherent representation of the outside world, and how information from the outside world is translated into appropriate actions.

Contact

  +61 7 334 69471

  ethan.scott@uq.edu.au

Group Publications

Research Areas

  • Sensory processing and integration
  • Calcium imaging and optogenetics
  • Biophotonics
  • Computational neuroscience

Group leader


Research Members


Students

Brain-wide sensory networks

We have investigated whole-brain neuronal responses in vivo at the cellular level to a range of sensory stimuli. This has enabled insight into the neuronal networks that enable zebrafish to process visual stimuli (Thompson et al 2016), auditory stimuli (Vanwalleghem et al. 2017, Poulsen et al. 2020), vestibular stimuli (Favre-Bulle et al. 2018) and water flow (Vanwalleghem et al. 2020).

Changes in sensory networks occurring in models of autism spectrum disorder

We have found the fmr1 model of autism spectrum disorder and fragile X syndrome exhibits differences in processing sensory information. Notably, zebrafish carrying the fmr1 mutation show differences in adaptive correlations between neuronal activity in the visual processing system during habituation, leading to slower habituation to visual stimuli (Marquez-Legoretta et al. 2019). We have also found increased transmission and reduced filtering in the auditory processing pathway in the fmr1 fish, leading to an auditory hypersensitivity phenotype which resembles that seen in humans with the fmr1 mutation (Constantin et al. 2019).

Optical trapping in vivo

Using optical trapping (focussed light to move objects), we have manipulated the otoliths (ear stones) of zebrafish in order to produce a fictive vestibular stimulus. This technique has allowed us to investigate the vestibular system of the fish while maintaining the brain motionless under the microscope objective. This has enabled us to characterise the vestibular processing network, and responses to stimulation of the right and left otoliths separately and together (Favre-Bulle et al. 2017 and 2018).

Visual pathways during escape behaviour

We uncovered the neural mechanisms underlying the escape response elicited by visual loom stimuli using several methods to give an in-depth understanding of functional connectivity in the network. We used fluorescent labelling to map neuronal projections between the thalamus and the tectum and characterised the activity of thalamic neurons with fluorescent calcium indicators. We then ablated the thalamo-tectal pathway in order to confirm its importance in generating escape responses to looms (Heap et al. 2018). We have also described the brain-wide patterns of activity that accompany habituation to visual looming stimuli, and have modelled the neural networks that perform this important form of sensory learning (Marquez-Legorreta et al, 2019)

 

2019

Lena Constantin, Rebecca E. Poulsen, Itia A. Favre-Bulle, Michael A. Taylor, Biao Sun, Geoffrey J. Goodhill, Gilles C. Vanwalleghem, and Ethan K. Scott (2019).
Altered brain-wide auditory networks in fmr1-mutant larval zebrafish.
bioRxiv.
URL: Constantin et al, 2019

Emmanuel Marquez-Legorreta, Lena Constantin, Marielle Piber, Itia A. Favre-Bulle, Michael A. Taylor, Gilles C. Vanwalleghem, and Ethan Scott (2019).
Brain-wide visual habituation networks in wild type and fmr1 zebrafish.
bioRxiv.
URL: Marquez-Legorreta et al, 2019

Itia A. Favre-Bulle, Alexander B. Stilgoe, Ethan K. Scott, and Halina Rubinsztein-Dunlop (2019).
Optical Trapping in vivo: Theory, Practice, and Applications.
Nanophotonics. 8 (6): 1023-1040. [IF 6.91].
URL: Favre-Bulle et al, 2019

Macarena Pavez, Adrian Thompson, Hayden Arnott, Camilla Mitchell, Ilaria D'Atri, Emily Don, John Chilton, Ethan Scott, John Lin, Kaylene Young, Robert Gasperini, and Lisa Foa (2019).
STIM1 is required for remodelling of the endoplasmic reticulum and microtubule cytoskeleton in steering growth cones.
The Journal of Neuroscience. 39 (26): 5095-5114. [IF 5.97].
URL: Pavez et al, 2019

2018

Itia Favre-Bulle, Gilles Vanwallehem, Michael Taylor, Halina Rubinsztein-Dunlop, and Ethan K. Scott (2018).
Cellular resolution imaging of vestibular processing across the larval zebrafish brain.
Current Biology, 28 (23): 3711-3722.
URL: Favre-Bulle et al, 2018.

Michael Taylor, Gilles Vanwalleghem, Itia Favre-Bulle, and Ethan K. Scott (2018).
Diffuse light-sheet microscopy for stripe-free imaging of neural populations.
Journal of Biophotonics. 11(12): 1-9.
URL: Taylor et al, 2018.

Lucy A.L. Heap, Gilles Vanwalleghem, Andrew W. Thompson, Itia A. Favre-Bulle, and Ethan K. Scott (2018). 
Luminance changes drive directional startle through a thalamic pathway.
Neuron. 99(2): 293-301.
URL: Heap et al, 2018.

Lucy Heap, Gilles Claude Vanwalleghem, Andrew Thompson, Itia Favre-Bulle, Halina Rubinsztein-Dunlop, and Ethan K Scott (2018).
Hypothalamic projections to the optic tectum in larval zebrafish.
Frontiers in Neuroanatomy, 11:135.
URL: Heap et al, 2018.

Gilles Vanwalleghem, Misha Ahrens, and Ethan K. Scott (2018).
Integrative whole-brain neuroscience in larval zebrafish.
Current Opinion in Neurobiology.  50: 136-145. 
URL: Vanwallaghem et al, 2018.

2017

Gilles Vanwalleghem, Lucy Heap, and Ethan K. Scott (2017). 
A profile of auditory-responsive neurons in the larval zebrafish brain.
Journal of Comparative Neurology, 525 (14): 3031-3043. 
URL: Vanwalleghem et al, 2017.

Itia Favre-Bulle, Alexander Stilgoe, Halina Rubinsztein-Dunlop, and Ethan Scott (2017).
Optical trapping of otoliths drives vetsibular behaviours in larval zebrafish.
Nature Communications 8: 630
URL: Favre-Bulle et al, 2017.

Lilach Avitan, Zac Pujic, Jan Molter, Matthew Van De Poll, Biao Sun, Haotian Teng, Rumelo Amor, Ethan Scott, and Geoffrey Goodhill (2017).

Spontaneous Activity in the Zebrafish Tectum Reorganizes over Development and Is Influenced by Visual Experience.
Current Biology, 27 (16): 2407-2419.
URL: Avitan et al, 2017.

2016

Andrew W. Thompson and Ethan K. Scott (2016).
Characterisation of sensitivity and orientation tuning for visually responsive ensembles in the zebrafish tectum.
Scientific Reports, 6 (3487): 1-10 
URL: Thompson et al, 2016.

Lilach Avitan, Zac Pujic, Nicholas Hughes, Ethan K. Scott, and Geoffrey J. Goodhill (2016).
Limitations of neural map topography for decoding spatial information.
The Journal of Neuroscience. 36 (19): 5385-5396. 
URL: Avitan et al, 2016.

Andrew W. Thompson, Gilles C. Vanwalleghem, Lucy A. Heap, and Ethan K. Scott (2016).
Functional profiles of visual, auditory, and water flow responsive neurons in the zebrafish tectum. 
Current Biology. 26: 1-12. 
URL: Thompson et al, 2016.

Kelsey Chalmers, Elizabeth M. Kita, Ethan K. Scott, and Geoffrey J. Goodhill (2016).
Quantitative analysis of axonal branch dynamics in the developing nervous system.
PLoS Computational Biology.  12 (3). 
URL: Chalmers et al, 2016.

2015

Itia A. Favre-Bulle, Daryl Preece, Timo A. Nieminen, Lucy A. Heap, Ethan K. Scott*, and Halina Rubinsztein-Dunlop* (*co-corresponding).
Scattering of Sculpted Light in Intact Brain Tissue, with Implications for Optogenetics.
Scientific Reports. 5: 11501. 
URL: Favre-Bulle et al, 2015.

Jacob H. Hines, Andrew R. Ravanelli, Rani Schwindt, Ethan K. Scott, and Bruce Appel (2015).
Activity-dependent competition for axon selection during myelination in vivo.
Nature Neuroscience. 18: 683-689. 
URL: Hines et al, 2015.

Geoffrey J. Goodhill, Richard A. Faville, Daniel J. Sutherland, Brendan A. Bicknell, Andrew W. Thompson, Zac Pujic, Biao Sun, Elizabeth M. Kita, and Ethan K. Scott (2015).
The dynamics of growth cone morphology. 
BMC Biology.  13:10. 
URL: Goodhill et al, 2015.

Elizabeth M. Kita , Ethan K. Scott, and Geoffrey J. Goodhill (2015).
The influence of activity on axon pathfinding in the optic tectum.
Developmental Neurobiology. Published online February 2015.
URL: Kita et al, 2015.

Elizabeth M. Kita , Ethan K. Scott, and Geoffrey J. Goodhill (2015).
Topographic wiring of the retinotectal connection in zebrafish.
Developmental Neurobiology. 75(6): 542-556.
URL: Kita et al, 2015.

2013

Lucy A. Heap, Chi-Ching Goh, Karin S. Kassahn, and Ethan K. Scott (2013).
Cerebellar output in zebrafish: an analysis of spatial patterns and topography in eurydendroid cell projections.
Frontiers in Neural Circuits.  7: 53.
URL: Heap et al. 2013

Hugh D. Simpson, Elizabeth M. Kita, Ethan K. Scott, and Geoffrey J. Goodhill (2013).
A quantitative analysis of branching, growth cone turning and directed growth in zebrafish retinotectal axon guidance.
Journal of Comparative Neurology.  521: 1409-1429.
URL: Simpson et al. 2013

2012

Isabel Formella, Ethan K. Scott, Tom H.J. Burne, Lauren R. Harms, Ashley Liu, Karly M. Turner, Xiaoying Cui, and Darryl W. Eyles (2012).
Transient Knockdown of Tyrosine Hydroxylase during Development Has Persistent Effects on Behaviour in Adult Zebrafish (Danio rerio).
PLoS One. 7 (8).
URL: Formella et al, 2012.

Joshua Simmich, Eric Staykov, and Ethan K. Scott (2012).
Zebrafish as an appealing model system for optogenetics.
Progress in Brain Research. 196: 145-162. 
URL: Simmich et al, 2012.

Phil McClenahan, Michael Troup, and Ethan K. Scott (2012).
Fin-tail Coordination During Escape and Predatory Behavior in Larval Zebrafish. 
PLoS One. 7(2). 
URL: McClenahan et al, 2012

2011

Thomas Burne, Ethan K. Scott, Bruno van Swinderen, Massimo Hilliard, Judith
Reinhard, Charles Claudianos, Darryl Eyles, and John McGrath (2011).
Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish?
Molecular Psychiatry. 16: 7-16. 
URL: Burne et al, 2011.

2010

Filippo Del Bene, Claire Wyart, Estuardo Robles, Amanda Tran, Loren Looger, Ethan K, Scott, Ehud Y. Isacoff, and Herwig Baier (2010).
Filtering of visual information in the tectum by an identified neural circuit.
Science. 330: 669-673.
URL: Del Bene et al, 2010.

Linda Nevin, Estuardo Robles, Herwig Baier, and Ethan K. Scott (2010).
Focusing on optic tectum circuitry through the lens of genetics.
BMC Biology. 8: 126.
URL: Nevin et al, 2010.

Shuichi Kani, Young-Ki Bae, Takashi Shimizu, Koji Tanabe, Chie Satoh, Mike Parsons,Ethan K. Scott, Shin-ichi Higashijima and Masahiko Hibi (2010).
Proneural gene-linked neurogenesis in zebrafish cerebellum.
Developmental Biology. 343 (1-2): 1-17.
URL: Kani et al, 2010.

2009

Claire Wyart, Filippo Del Bene, Erica Warp, Ethan K. Scott, Dirk Trauner, Herwig Baier and Ehud Isacoff (2009).
Optogenetic dissection of a behavioural module in the vertebrate spinal cord.
Nature. 461: 407-410. 
URL: Wyart et al, 2009.

Herwig Baier and Ethan K. Scott (2009).
Optics and genetics cross paths in the zebrafish nervous system.
Current Opinions in Neurobiology. 19(5): 553-560. 
URL: Baier and Scott, 2009.

Ethan K. Scott and Herwig Baier (2009).
The cellular architecture of the larval zebrafish tectum, as revealed by Gal4 enhancer trap lines.
Frontiers in Neural Circuits. 3(13).
URL: Scott and Baier, 2009.

Ethan K. Scott (2009).
The Gal4/UAS toolbox in zebrafish: New approaches for defining behavioral circuits.
Journal of Neurochemistry. 110(2): 441-456.
URL: Scott, 2009. 

Lisette A. Maddison, Jainjun Lu, Tristan Victoroff, Ethan K. Scott, Herwig Baier, and Wenbiao Chen. (2009).
A gain-of-function screen in zebrafish identifies a guanylate cyclase with a role in neuronal degeneration.
Molecular Genetics and Genomics. 281(5): 551-563.
URL: Maddison et al, 2009.

2007

Stephanie Szobota, Pau Gorostiza, Filippo Del Bene, Claire Wyart, Doris L. Fortin, Kate Kolstad, Orapim Tulyathan, Matthew Volgraf, Rika Numano, Holly Aaron, Ethan K. Scott, Richard Kramer, John Flannery, Herwig Baier, Dirk Trauner and Ehud Isacoff (2007).
Remote control of neuronal activity with a light-gated glutamate receptor.
Neuron. 54(4): 535-545.
URL: Szobota et al, 2007.

Ethan K. Scott, Lindsay Mason, Aristides B. Arrenberg, Limor Ziv, Nathan J. Gosse, Tong Xiao, Neil C. Chi, Kazuhide Asakawa, Koichi Kawakami, and Herwig Baier (2007).
Targeting neural circuitry in zebrafish using GAL4 enhancer trapping.
Nature Methods. 4(4): 323-326.
URL: Scott et al, 2007.

Our lab spans numerous experimental approaches and techniques, and as a result, we need all kinds of expertise. The core of our lab comprises neuroscientists with interests including developmental neuroscience, circuit function, and behaviour, and we are always looking to add motivated researchers of this type. Increasingly, experience with coding (Matlab and Python) is desirable, but for the right candidate, this can be learned after arriving in the lab.

Our whole-brain imaging experiments require that we custom build our light-sheet microscopes with unique capabilities.  Additionally, our optogenetics experiments require bespoke holograms within the brains of our live animals. Finally, our vestibular experiments require the optical trapping of large objects in vivo during calcium imaging. We are constantly developing and refining innovative optical physics approaches, and are always looking to recruit skilled physicists and engineers to our team.

With our light-sheet microscopes, we produce vast datasets containing activity from hundreds of thousands or millions of neurons. This leaves us with a great need for people who can code solutions for image analysis, data mining, and the detection of salient patterns among these vast data. Our mathematical and neuroinformatic approaches have grown more sophisticated over the years (see the progression from Thompson et al, 2016 to Vanwalleghem et al, 2017Favre-Bulle et al, 2018, and Marquez-Legorreta et al, 2019), but we are constantly seeking new and better ways to make sense of brain-wide neural function from a computational standpoint. We welcome applications from researchers interested in explaining neural activity mathematically or in developing testable mathematical models for sensory processing.

Lab positions

Positions are available across our research program for undergraduates, honours students, PhD students, and postdocs, and we are happy to entertain new ideas. If you are interested in joining the lab, please contact Ethan, providing a CV and ideas for the type of project that you would like to carry out.