Brain-wide circuitry underlying altered auditory habituation in zebrafish models of autism.

Auditory processing is widely understood to occur differently in autism, though the patterns of brain activity underlying these differences are not well understood. The diversity of autism also means brain-wide networks may change in various ways to produce similar behavioral outputs. We used larval zebrafish to investigate auditory habituation in four genetic lines relevant to autism: , , and .

Valproic acid-induced teratogenicity is driven by senescence and prevented by Rapamycin in human spinal cord and animal models.

Valproic acid (VPA) is an effective and widely used anti-seizure medication but is teratogenic when used during pregnancy, affecting brain and spinal cord development for reasons that remain largely unclear. Here we designed a genetic recombinase-based SOX10 reporter system in human pluripotent stem cells that enables tracking and lineage tracing of Neural Crest cells (NCCs) in a human organoid model of the developing neural tube. We found that VPA induces extensive cellular senescence and promotes mesenchymal differentiation of human NCCs.

Probabilistic modeling reveals coordinated social interaction states and their multisensory bases.

Social behavior across animal species ranges from simple pairwise interactions to thousands of individuals coordinating goal-directed movements. Regardless of the scale, these interactions are governed by the interplay between multimodal sensory information and the internal state of each animal. Here, we investigate how animals use multiple sensory modalities to guide social behavior in the highly social zebrafish () and uncover the complex features of pairwise interactions early in development.

Probabilistic modeling reveals coordinated social interaction states and their multisensory bases.

Social behavior across animal species ranges from simple pairwise interactions to thousands of individuals coordinating goal-directed movements. Regardless of the scale, these interactions are governed by the interplay between multimodal sensory information and the internal state of each animal. Here, we investigate how animals use multiple sensory modalities to guide social behavior in the highly social zebrafish () and uncover the complex features of pairwise interactions early in development.

The Visual Systems of Zebrafish.

The zebrafish visual system has become a paradigmatic preparation for behavioral and systems neuroscience. Around 40 types of retinal ganglion cells (RGCs) serve as matched filters for stimulus features, including light, optic flow, prey, and objects on a collision course. RGCs distribute their signals via axon collaterals to 12 retinorecipient areas in forebrain and midbrain.

Brain-wide impacts of sedation on spontaneous activity and auditory processing in larval zebrafish.

Unlabelled: Despite their widespread use, we have limited knowledge of the mechanisms by which sedatives mediate their effects on brain-wide networks. This is, in part, due to the technical challenge of observing activity across large populations of neurons in normal and sedated brains. In this study, we examined the effects of the sedative dexmedetomidine, and its antagonist atipamezole, on spontaneous brain dynamics and auditory processing in zebrafish larvae.

From calcium imaging to graph topology.

Systems neuroscience is facing an ever-growing mountain of data. Recent advances in protein engineering and microscopy have together led to a paradigm shift in neuroscience; using fluorescence, we can now image the activity of every neuron through the whole brain of behaving animals. Even in larger organisms, the number of neurons that we can record simultaneously is increasing exponentially with time.

Auditory processing in rodent models of autism: a systematic review.

Autism is a complex condition with many traits, including differences in auditory sensitivity. Studies in human autism are plagued by the difficulty of controlling for aetiology, whereas studies in individual rodent models cannot represent the full spectrum of human autism. This systematic review compares results in auditory studies across a wide range of established rodent models of autism to mimic the wide range of aetiologies in the human population.

Optical tweezers across scales in cell biology.

Optical tweezers (OT) provide a noninvasive approach for delivering minute physical forces to targeted objects. Controlling such forces in living cells or in vitro preparations allows for the measurement and manipulation of numerous processes relevant to the form and function of cells. As such, OT have made important contributions to our understanding of the structures of proteins and nucleic acids, the interactions that occur between microscopic structures within cells, the choreography of complex processes such as mitosis, and the ways in which cells interact with each other.

Brain-wide visual habituation networks in wild type and fmr1 zebrafish.

Habituation is a form of learning during which animals stop responding to repetitive stimuli, and deficits in habituation are characteristic of several psychiatric disorders. Due to technical challenges, the brain-wide networks mediating habituation are poorly understood. Here we report brain-wide calcium imaging during larval zebrafish habituation to repeated visual looming stimuli.

Contributions of Luminance and Motion to Visual Escape and Habituation in Larval Zebrafish.

Animals from insects to humans perform visual escape behavior in response to looming stimuli, and these responses habituate if looms are presented repeatedly without consequence. While the basic visual processing and motor pathways involved in this behavior have been described, many of the nuances of predator perception and sensorimotor gating have not. Here, we have performed both behavioral analyses and brain-wide cellular-resolution calcium imaging in larval zebrafish while presenting them with visual loom stimuli or stimuli that selectively deliver either the movement or the dimming properties of full loom stimuli.

RNA-induced inflammation and migration of precursor neurons initiates neuronal circuit regeneration in zebrafish.

Tissue regeneration and functional restoration after injury are considered as stem- and progenitor-cell-driven processes. In the central nervous system, stem cell-driven repair is slow and problematic because function needs to be restored rapidly for vital tasks. In highly regenerative vertebrates, such as zebrafish, functional recovery is rapid, suggesting a capability for fast cell production and functional integration.

The tectum/superior colliculus as the vertebrate solution for spatial sensory integration and action.

The superior colliculus, or tectum in the case of non-mammalian vertebrates, is a part of the brain that registers events in the surrounding space, often through vision and hearing, but also through electrosensation, infrared detection, and other sensory modalities in diverse vertebrate lineages. This information is used to form maps of the surrounding space and the positions of different salient stimuli in relation to the individual. The sensory maps are arranged in layers with visual input in the uppermost layer, other senses in deeper positions, and a spatially aligned motor map in the deepest layer.

Broad frequency sensitivity and complex neural coding in the larval zebrafish auditory system.

Most animals have complex auditory systems that identify salient features of the acoustic landscape to direct appropriate responses. In fish, these features include the volume, frequency, complexity, and temporal structure of acoustic stimuli transmitted through water. Larval fish have simple brains compared to adults but swim freely and depend on sophisticated sensory processing for survival.

Calcium Imaging and the Curse of Negativity.

The imaging of neuronal activity using calcium indicators has become a staple of modern neuroscience. However, without ground truths, there is a real risk of missing a significant portion of the real responses. Here, we show that a common assumption, the non-negativity of the neuronal responses as detected by calcium indicators, biases all levels of the frequently used analytical methods for these data.

Optical Tweezers Exploring Neuroscience.

Over the past decade, optical tweezers (OT) have been increasingly used in neuroscience for studies of molecules and neuronal dynamics, as well as for the study of model organisms as a whole. Compared to other areas of biology, it has taken much longer for OT to become an established tool in neuroscience. This is, in part, due to the complexity of the brain and the inherent difficulties in trapping individual molecules or manipulating cells located deep within biological tissue.

Sound generation in zebrafish with Bio-Opto-Acoustics.

Hearing is a crucial sense in underwater environments for communication, hunting, attracting mates, and detecting predators. However, the tools currently used to study hearing are limited, as they cannot controllably stimulate specific parts of the auditory system. To date, the contributions of hearing organs have been identified through lesion experiments that inactivate an organ, making it difficult to gauge the specific stimuli to which each organ is sensitive, or the ways in which inputs from multiple organs are combined during perception.

Multiscale imaging of basal cell dynamics in the functionally mature mammary gland.

The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of milk from alveolar units and its passage along the mammary ductal network.

Altered brain-wide auditory networks in a zebrafish model of fragile X syndrome.

Background: Loss or disrupted expression of the FMR1 gene causes fragile X syndrome (FXS), the most common monogenetic form of autism in humans. Although disruptions in sensory processing are core traits of FXS and autism, the neural underpinnings of these phenotypes are poorly understood. Using calcium imaging to record from the entire brain at cellular resolution, we investigated neuronal responses to visual and auditory stimuli in larval zebrafish, using fmr1 mutants to model FXS.

Brain-Wide Mapping of Water Flow Perception in Zebrafish.

Information about water flow, detected by lateral line organs, is critical to the behavior and survival of fish and amphibians. While certain aspects of water flow processing have been revealed through electrophysiology, we lack a comprehensive description of the neurons that respond to water flow and the network that they form. Here, we use brain-wide calcium imaging in combination with microfluidic stimulation to map out, at cellular resolution, neuronal responses involved in perceiving and processing water flow information in larval zebrafish.

STIM1 Is Required for Remodeling of the Endoplasmic Reticulum and Microtubule Cytoskeleton in Steering Growth Cones.

The spatial and temporal regulation of calcium signaling in neuronal growth cones is essential for axon guidance. In growth cones, the endoplasmic reticulum (ER) is a significant source of calcium signals. However, it is not clear whether the ER is remodeled during motile events to localize calcium signals in steering growth cones.

Cellular-Resolution Imaging of Vestibular Processing across the Larval Zebrafish Brain.

The vestibular system, which reports on motion and gravity, is essential to postural control, balance, and egocentric representations of movement and space. The motion needed to stimulate the vestibular system complicates studying its circuitry, so we previously developed a method for fictive vestibular stimulation in zebrafish, using optical trapping to apply physical forces to the otoliths. Here, we combine this approach with whole-brain calcium imaging at cellular resolution, delivering a comprehensive map of the brain regions and cellular responses involved in basic vestibular processing.

Luminance Changes Drive Directional Startle through a Thalamic Pathway.

Looming visual stimuli result in escape responses that are conserved from insects to humans. Despite their importance for survival, the circuits mediating visual startle have only recently been explored in vertebrates. Here we show that the zebrafish thalamus is a luminance detector critical to visual escape.

Diffuse light-sheet microscopy for stripe-free calcium imaging of neural populations.

Light-sheet microscopy is used extensively in developmental biology and neuroscience. One limitation of this approach is that absorption and scattering produces shadows in the illuminating light sheet, resulting in stripe artifacts. Here, we introduce diffuse light-sheet microscopes that use a line diffuser to randomize the light propagation within the image plane, allowing the light sheets to reform after obstacles.