Visual systems have evolved to discriminate between different wavelengths of light. The ability to perceive color, or specific light wavelengths, is important as color conveys crucial information about both biotic and abiotic features in the environment. Indeed, different wavelengths of light can drive distinct patterns of activity in the vertebrate brain, yet what remains incompletely understood is whether distinct wavelengths can invoke etiologically relevant behavioral changes.
View Article and Find Full Text PDFMany genes are known to regulate retinal regeneration after widespread tissue damage. Conversely, genes controlling regeneration after limited cell loss, as per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important.
View Article and Find Full Text PDFAs essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, gs homeobox 1 (gsx1), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus.
View Article and Find Full Text PDFUnlabelled: Many genes are known to regulate retinal regeneration following widespread tissue damage. Conversely, genes controlling regeneration following limited retinal cell loss, akin to disease conditions, are undefined. Combining a novel retinal ganglion cell (RGC) ablation-based glaucoma model, single cell omics, and rapid CRISPR/Cas9-based knockout methods to screen 100 genes, we identified 18 effectors of RGC regeneration kinetics.
View Article and Find Full Text PDFAnimal behavior, from simple to complex, is dependent on the faithful wiring of neurons into functional neural circuits. Neural circuits undergo dramatic experience-dependent remodeling during brief developmental windows called critical periods. Environmental experience during critical periods of plasticity produces sustained changes to circuit function and behavior.
View Article and Find Full Text PDFSensory experience instructs neurodevelopment and refines sensory processing. Here, we describe a minimally invasive protocol to immobilize zebrafish during early development to control visual experience. We describe how to prepare larvae for embedding in agarose at two separate timepoints in development.
View Article and Find Full Text PDFOne of the greatest expenses in running a zebrafish laboratory is the aquatic systems used for housing. These critical pieces of equipment are essential and incorporate components undergoing constant activity in pumping water, monitoring, dosing, and filtration. The systems available on the market are robust, yet ongoing activity eventually leads to the need for repair or replacement.
View Article and Find Full Text PDFBrain laterality is a prominent feature in Bilateria, where neural functions are favored in a single brain hemisphere. These hemispheric specializations are thought to improve behavioral performance and are commonly observed as sensory or motor asymmetries, such as handedness in humans. Despite its prevalence, our understanding of the neural and molecular substrates instructing functional lateralization is limited.
View Article and Find Full Text PDFDuring the visual critical period (CP), sensory experience refines the structure and function of visual circuits. The basis of this plasticity was long thought to be limited to cortical circuits, but recently described thalamic plasticity challenges this dogma and demonstrates greater complexity underlying visual plasticity. Yet how visual experience modulates thalamic neurons or how the thalamus modulates CP timing is incompletely understood.
View Article and Find Full Text PDFThe Musashi proteins, MSI1 and MSI2, are conserved RNA binding proteins with a role in the maintenance and renewal of stem cells. Contrasting with this role, terminally differentiated photoreceptor cells express high levels of MSI1 and MSI2, pointing to a role for the two proteins in vision. Combined knockout of Msi1 and Msi2 in mature photoreceptor cells abrogated the retinal response to light and caused photoreceptor cell death.
View Article and Find Full Text PDFThe increased abuse of novel drugs has created a critical need for cheap and rapid in vivo models to understand whole organism drug-induced toxicity and metabolic impacts. One such model is zebrafish, which share many similarities to human. Assays have been developed for behavioral, toxicity, and metabolism elucidation following chemical exposure.
View Article and Find Full Text PDFAsymmetries in motor behavior, such as human hand preference, are observed throughout bilateria. However, neural substrates and developmental signaling pathways that impose underlying functional lateralization on a broadly symmetric nervous system are unknown. Here we report that in the absence of over-riding visual information, zebrafish larvae show intrinsic lateralized motor behavior that is mediated by a cluster of 60 posterior tuberculum (PT) neurons in the forebrain.
View Article and Find Full Text PDFLarge-scale genomic studies have recently identified genetic variants causative for major neurodevelopmental disorders, such as intellectual disability and autism. However, determining how underlying developmental processes are affected by these mutations remains a significant challenge in the field. Zebrafish is an established model system in developmental neurogenetics that may be useful in uncovering the mechanisms of these mutations.
View Article and Find Full Text PDFAtlases provide a framework for spatially mapping information from diverse sources into a common reference space. Specifically, brain atlases allow annotation of gene expression, cell morphology, connectivity, and activity. In larval zebrafish, advances in genetics, imaging, and computational methods now allow the collection of such information brain-wide.
View Article and Find Full Text PDFBackground: Animals use sensory cues to efficiently locate resources, but when sensory information is insufficient, they may rely on internally coded search strategies. Despite the importance of search behavior, there is limited understanding of the underlying neural mechanisms in vertebrates.
Results: Here, we report that loss of illumination initiates sophisticated light-search behavior in larval zebrafish.
Proc Natl Acad Sci U S A
January 2017
Skeletal muscle contractions are initiated by an increase in Ca released during excitation-contraction (EC) coupling, and defects in EC coupling are associated with human myopathies. EC coupling requires communication between voltage-sensing dihydropyridine receptors (DHPRs) in transverse tubule membrane and Ca release channel ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum (SR). Stac3 protein (SH3 and cysteine-rich domain 3) is an essential component of the EC coupling apparatus and a mutation in human STAC3 causes the debilitating Native American myopathy (NAM), but the nature of how Stac3 acts on the DHPR and/or RyR1 is unknown.
View Article and Find Full Text PDFAdvances in genetic technologies enable the highly selective expression of transgenes in targeted neuronal cell types. Transgene expression can be used to noninvasively ablate, silence or activate neurons, providing a tool to probe their contribution to the control of behavior or physiology. Here, we describe the use of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel Nav1.
View Article and Find Full Text PDFOver the course of each day, animals prioritize different objectives. Immediate goals may reflect fluctuating internal homeostatic demands, prompting individuals to seek out energy supplies or warmth. At other times, the environment may present temporary challenges or opportunities.
View Article and Find Full Text PDFThe zebrafish model is an emerging system for the study of neuromuscular disorders. In the study of neuromuscular diseases, the integrity of the muscle membrane is a critical disease determinant. To date, numerous neuromuscular conditions display degenerating muscle fibers with abnormal membrane integrity; this is most commonly observed in muscular dystrophies.
View Article and Find Full Text PDFMany genetic manipulations are limited by difficulty in obtaining adequate levels of protein expression. Bioinformatic and experimental studies have identified nucleotide sequence features that may increase expression, however it is difficult to assess the relative influence of these features. Zebrafish embryos are rapidly injected with calibrated doses of mRNA, enabling the effects of multiple sequence changes to be compared in vivo.
View Article and Find Full Text PDFRapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs).
View Article and Find Full Text PDFDuchenne muscular dystrophy (DMD) is a common and relentlessly progressive muscle disease. Some interventions have been identified that modestly slow progression and prolong survival, but more meaningful therapies are lacking. The goal of this study is to identify new therapeutic pathways for DMD using a zebrafish model of the disease.
View Article and Find Full Text PDFThe zebrafish has proven to be a valuable model system for exploring skeletal muscle function and for studying human muscle diseases. Despite the many advantages offered by in vivo analysis of skeletal muscle in the zebrafish, visualizing the complex and finely structured protein milieu responsible for muscle function, especially in whole embryos, can be problematic. This hindrance stems from the small size of zebrafish skeletal muscle (60 μm) and the even smaller size of the sarcomere.
View Article and Find Full Text PDFAn essential step in muscle fiber maturation is the assembly of highly ordered myofibrils that are required for contraction. Much remains unknown about the molecular mechanisms governing the formation of the contractile apparatus. We identified an early embryonic motility mutant in zebrafish caused by integration of a transgene into the pseudophosphatase dual specificity phosphatase 27 (dusp27) gene.
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