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Hildebrand, David

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Hildebrand

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Hildebrand, David
Author's Publications: search.filters.isAuthorOfPublication.37373e6d-64a3-4837-8c68-1340e2ab3f02

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    Sensorimotor computation underlying phototaxis in zebrafish
    (Nature Publishing Group UK, 2017) Wolf, Sébastien; Dubreuil, Alexis M.; Bertoni, Tommaso; Böhm, Urs Lucas; Bormuth, Volker; Candelier, Raphaël; Karpenko, Sophia; Hildebrand, David; Bianco, Isaac H.; Monasson, Rémi; Debrégeas, Georges
    Animals continuously gather sensory cues to move towards favourable environments. Efficient goal-directed navigation requires sensory perception and motor commands to be intertwined in a feedback loop, yet the neural substrate underlying this sensorimotor task in the vertebrate brain remains elusive. Here, we combine virtual-reality behavioural assays, volumetric calcium imaging, optogenetic stimulation and circuit modelling to reveal the neural mechanisms through which a zebrafish performs phototaxis, i.e. actively orients towards a light source. Key to this process is a self-oscillating hindbrain population (HBO) that acts as a pacemaker for ocular saccades and controls the orientation of successive swim-bouts. It further integrates visual stimuli in a state-dependent manner, i.e. its response to visual inputs varies with the motor context, a mechanism that manifests itself in the phase-locked entrainment of the HBO by periodic stimuli. A rate model is developed that reproduces our observations and demonstrates how this sensorimotor processing eventually biases the animal trajectory towards bright regions.
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    Lamellar projections in the endolymphatic sac act as a relief valve to regulate inner ear pressure
    (eLife Sciences Publications, Ltd, 2018) Swinburne, Ian; Mosaliganti, Kishore R; Upadhyayula, Srigokul; Liu, Tsung-Li; Hildebrand, David; Tsai, Tony Y -C; Chen, Anzhi; Al-Obeidi, Ebaa; Fass, Anna K; Malhotra, Samir; Engert, Florian; Lichtman, Jeff; Kirchausen, Tomas; Betzig, Eric; Megason, Sean
    The inner ear is a fluid-filled closed-epithelial structure whose function requires maintenance of an internal hydrostatic pressure and fluid composition. The endolymphatic sac (ES) is a dead-end epithelial tube connected to the inner ear whose function is unclear. ES defects can cause distended ear tissue, a pathology often seen in hearing and balance disorders. Using live imaging of zebrafish larvae, we reveal that the ES undergoes cycles of slow pressure-driven inflation followed by rapid deflation. Absence of these cycles in lmx1bb mutants leads to distended ear tissue. Using serial-section electron microscopy and adaptive optics lattice light-sheet microscopy, we find a pressure relief valve in the ES comprised of partially separated apical junctions and dynamic overlapping basal lamellae that separate under pressure to release fluid. We propose that this lmx1-dependent pressure relief valve is required to maintain fluid homeostasis in the inner ear and other fluid-filled cavities.
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    Imaging ATUM ultrathin section libraries with WaferMapper: a multi-scale approach to EM reconstruction of neural circuits
    (Frontiers Media S.A., 2014) Hayworth, Kenneth J.; Morgan, Josh L.; Schalek, Richard; Berger, Daniel; Hildebrand, David; Lichtman, Jeff
    The automated tape-collecting ultramicrotome (ATUM) makes it possible to collect large numbers of ultrathin sections quickly—the equivalent of a petabyte of high resolution images each day. However, even high throughput image acquisition strategies generate images far more slowly (at present ~1 terabyte per day). We therefore developed WaferMapper, a software package that takes a multi-resolution approach to mapping and imaging select regions within a library of ultrathin sections. This automated method selects and directs imaging of corresponding regions within each section of an ultrathin section library (UTSL) that may contain many thousands of sections. Using WaferMapper, it is possible to map thousands of tissue sections at low resolution and target multiple points of interest for high resolution imaging based on anatomical landmarks. The program can also be used to expand previously imaged regions, acquire data under different imaging conditions, or re-image after additional tissue treatments.
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    Whole-brain functional and structural examination in larval zebrafish
    (2015-04-21) Hildebrand, David; Uchida, Naoshige; Harvey, Christopher; Kasthuri, Narayanan
    Comprehending how neuronal networks compute is a central goal in neuroscience, but it is challenging to directly measure how information flows through and is processed by large circuits of interconnected neurons. Ideally, one would capture what every neuron represents and determine which of its counterparts this information was shared with. However, measuring neuronal activity requires high temporal resolution and finding the connections between neurons requires high spatial resolution. The constraints imposed by current techniques for evaluating neuronal population activity and network anatomy put these requirements at odds: those that sample rapidly typically do so with lower spatial resolution, while those that provide high spatial resolution generally sample slowly. Finding ways to combine the strengths of different approaches and applying them to relatively small nervous systems holds great potential for examining neuronal network function. The translucence, genetic toolset, and small size of the larval zebrafish model organism make it ideal for whole-brain activity mapping at cellular resolution while presenting sensory stimuli and recording behavior. Constant improvements to reporters of neuronal activity and light microscope designs are being made to capture snapshots of neuronal activity more rapidly. However, existing methods for identifying neuronal connectivity in larval zebrafish are applicable to only a small fraction of the population at once. An efficient way to determine the neuronal network anatomy—or wiring diagram—of a circuit is to reconstruct connections from micrographs of continuous series of thin sections acquired with electron microscopy, but this technique has yet to be applied to studying neuronal circuits in larval zebrafish. Furthermore, its use has not yet approached the scale of the complete larval zebrafish brain. This dissertation describes new tools for enhancing larval zebrafish activity mapping endeavors and the development of a serial-section electron microscopy approach to accomplish dense structural imaging of the complete brain. Together, these developments provide a foundation for studying neuronal network computation in the context of a behaving animal.
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    Geometric Deep Learning Enables 3D Kinematic Profiling Across Species and Environments
    (Springer Science and Business Media LLC, 2021-04-19) Dunn, Timothy; Marshall, Jesse; Severson, Kyle S.; Aldarondo, Diego; Hildebrand, David; Chettih, Selmaan; Wang, William; Gellis, Amanda; Carlson, David E.; Aronov, Dmitriy; Freiwald, Winrich; Wang, Fan; Ölveczky, Bence P.
    Comprehensive descriptions of animal behavior require precise measurements of 3D whole-body movements. Although 2D approaches can track visible landmarks in restrictive environments, performance drops significantly in freely moving animals, where occlusions and appearance changes are ubiquitous. To enable robust 3D tracking, we designed DANNCE, a method using projective geometry to construct inputs to a convolutional neural network that leverages learned 3D geometric reasoning to track anatomical landmarks across species and behaviors. We trained and benchmarked DANNCE using a new 7-million frame dataset relating color videos and rodent 3D poses. In rats and mice, DANNCE robustly tracked dozens of landmarks on the head, trunk, and limbs of freely moving animals in naturalistic settings, achieving over an order of magnitude better accuracy than prior techniques. We extend DANNCE to rat pups, marmosets, and chickadees, and demonstrate a novel ability to quantitatively profile behavioral lineage over development. DANNCE offers unprecedented analytical access to animal behavior across species and environments.