Light wavelength modulates search behavior performance in zebrafish.

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. To address how specific wavelengths in the visible spectrum modulate behavioral performance, we use larval zebrafish and a stereotypic light-search behavior. Prior work has shown that the cessation of light triggers a transitional light-search behavior, which we use to interrogate wavelength-dependent behavioral modulation. Using 8 narrow spectrum light sources in the visible range, we demonstrate that all wavelengths induce motor parameters consistent with search behavior, yet the magnitude of search behavior is spectrum sensitive and the underlying motor parameters are modulated in distinct patterns across short, medium, and long wavelengths. However, our data also establishes that not all motor features of search are impacted by wavelength. To define how wavelength modulates search performance, we performed additional assays with alternative wavelengths, dual wavelengths, and variable intensity. Last, we also tested blind larvae to resolve which components of wavelength dependent behavioral changes potentially include signaling from non-retinal photoreception. These findings have important implications as organisms can be exposed to varying wavelengths in laboratory and natural settings and therefore impose unique behavioral outputs.

Developmental Neurotoxicity and Behavioral Screening in Larval Zebrafish with a Comparison to Other Published Results.

With the abundance of chemicals in the environment that could potentially cause neurodevelopmental deficits, there is a need for rapid testing and chemical screening assays. This study evaluated the developmental toxicity and behavioral effects of 61 chemicals in zebrafish (Danio rerio) larvae using a behavioral Light/Dark assay. Larvae (n = 16-24 per concentration) were exposed to each chemical (0.0001-120 µM) during development and locomotor activity was assessed. Approximately half of the chemicals (n = 30) did not show any gross developmental toxicity (i.e., mortality, dysmorphology or non-hatching) at the highest concentration tested. Twelve of the 31 chemicals that did elicit developmental toxicity were toxic at the highest concentration only, and thirteen chemicals were developmentally toxic at concentrations of 10 µM or lower. Eleven chemicals caused behavioral effects; four chemicals (6-aminonicotinamide, cyclophosphamide, paraquat, phenobarbital) altered behavior in the absence of developmental toxicity. In addition to screening a library of chemicals for developmental neurotoxicity, we also compared our findings with previously published results for those chemicals. Our comparison revealed a general lack of standardized reporting of experimental details, and it also helped identify some chemicals that appear to be consistent positives and negatives across multiple laboratories.

Environmental and Molecular Modulation of Motor Individuality in Larval Zebrafish.

Innate behavioral biases such as human handedness are a ubiquitous form of inter-individual variation that are not strictly hardwired into the genome and are influenced by diverse internal and external cues. Yet, genetic and environmental factors modulating behavioral variation remain poorly understood, especially in vertebrates. To identify genetic and environmental factors that influence behavioral variation, we take advantage of larval zebrafish light-search behavior. During light-search, individuals preferentially turn in leftward or rightward loops, in which directional bias is sustained and non-heritable. Our previous work has shown that bias is maintained by a habenula-rostral PT circuit and genes associated with Notch signaling. Here we use a medium-throughput recording strategy and unbiased analysis to show that significant individual to individual variation exists in wildtype larval zebrafish turning preference. We classify stable left, right, and unbiased turning types, with most individuals exhibiting a directional preference. We show unbiased behavior is not due to a loss of photo-responsiveness but reduced persistence in same-direction turning. Raising larvae at elevated temperature selectively reduces the leftward turning type and impacts rostral PT neurons, specifically. Exposure to conspecifics, variable salinity, environmental enrichment, and physical disturbance does not significantly impact inter-individual turning bias. Pharmacological manipulation of Notch signaling disrupts habenula development and turn bias individuality in a dose dependent manner, establishing a direct role of Notch signaling. Last, a mutant allele of a known Notch pathway affecter gene, gsx2, disrupts turn bias individuality, implicating that brain regions independent of the previously established habenula-rostral PT likely contribute to inter-individual variation. These results establish that larval zebrafish is a powerful vertebrate model for inter-individual variation with established neural targets showing sensitivity to specific environmental and gene signaling disruptions. Our results provide new insight into how variation is generated in the vertebrate nervous system.