We are interested in addressing how the brain perceives and integrates information about the outside world, and we have expanded our experiments to cover as many sensory modalities as possible.  Most of these projects have been based around calcium imaging in large populations of neurons (the whole brain in some cases), followed by further anatomical or functional analyses of the neurons involved.

Vision

In the visual system, we have characterised the tuning of neurons in the tectum to visual stimuli with different levels of saliency (Thompson et al, 2016).  We have also used calcium imaging, anatomical mapping, ablation experiments, and behavioural analyses to describe a role for the thalamus in detecting changes in luminance, and have described how this information contributes to the likelihood and the direction of escape behaviours in larval zebrafish presented with a threatening visual stimulus (Heap et al, 2018). We remain interested in projects that will further expand our understanding of the cell types and circuits involved in visual processing.

Visual learning

Habituation is simple form of learning by which responses to a given stimulus decrease with repetitive presentation of the stimulus. By using a loom stimulus to elicit habituation in larval zebrafish, we have described several brain circuits involved in this process: different populations of neurons in different parts of the visual and sensorimotor pathways show distinct response patterns and degrees of habituation. This was the first description of a visual learning network across the whole brain at cellular resolution (Marquez-Legoretta et al., 2019). We are now expanding this work to include comparisons of the neurons involved in habituation with those that mediate perception of looming stimuli in naïve animals.

Audition

We have recently published the first whole-brain analysis of auditory processing in larval zebrafish, indicating that it is rudimentary in terms of frequency discrimination and tonotopy in larvae.  These auditory responses are, however, useful to characterise, as this now puts us in a position to combine auditory stimuli with stimuli from other modalities in studies of sensory integration (Vanwalleghem et al., 2017). We are also interested in the details of auditory stimuli that larval zebrafish can distinguish, and the brain regions and cell types involved in frequency discrimination and the perception of other key features of auditory stimuli (Poulsen et al., 2020).

Water flow

To study the perception of water flow, we have designed a microfluidics device capable of delivering controlled flow over the trunk of larvae while they remain stationary for calcium imaging.  This permits us to observe the neurons in the brain that respond to water flow, their response properties when the direction or strength of the flow changes, and their locations within the brain.  This will allow us to build models of how flow is perceived in the early stages of this pathway, and how emergent properties, such as representations of accumulated flow over time, arise later in the sensory processing cascade. This basic description has recently been published (Vanwalleghem et al, 2020), and we are now interested in exploring the finer nuances of the system.

Vestibular motion

Our work in the vestibular system is aimed at addressing one of the fundamental challenges to studying this modality: vestibular stimuli necessarily move the subject, and this makes most approaches for studying activity (electrophysiology, fMRI, calcium imaging) difficult or impossible.  Using the physics technique of optical trapping, we have applied forces to the otoliths (ear stones) of immobilised zebrafish larvae, tricking them into thinking that they are moving when they are stationary.  This permits us to perform calcium imaging to reveal the cells and circuits involved in vestibular processing.  The optical physics and behaviour for this approach are described in (Favre-Bulle et al, 2017) and our description of the brain-wide vestibular processing is (Favre-Bulle et al, 2018). Building on this work, we are now testing brain-wide responses to unilateral and bilateral auditory stimulation, describing the unique and overlapping contributions made by different types of otolith, and exploring how directional hearing may emerge in this small brain.

Sensory integration and learning

As we further refine our techniques for stimulating a range of sensory modalities and get baseline data for how each modality is processed in the brain’s circuits, we are shifting our attention to important biological questions that are made accessible by these techniques.  These include how information from different modalities influence one another and are integrated, how habituation and attention are manifested in this circuitry, and how their circuits change in models of human sensory disorders.

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