Zebrafish: from genes and neurons to circuits, behavior and disease

The Journal of Neurogenetics presents this special issue entitled ‘Zebrafish: From Genes and Neurons to Circuits, Behavior and Disease’. We invited colleagues using the zebrafish model in the areas of sensory and motor systems, neural circuits, and central nervous system (CNS) disorders to contribute reviews of recent studies or original work to this issue. The primary goal of this special issue is to highlight the importance of the zebrafish model for advances in the genetics and molecular analyses of sensory systems and for understanding the genes and circuits underlying simple motor and more complex behaviors.

Linking genes to behavior and the function of the nervous system has been a long standing goal in neuroscience. Notably, the zebrafish has been increasing in popularity as a vertebrate model to address fundamental questions in neuroscience. The major appeal of zebrafish is the ease of genetic manipulations and transgenesis, and the transparency of the fish at early stages. With the possibility of (i) large-scale mutagenesis screens and (ii) CRISPR technology, along with (iii) transcriptomic approaches to identify molecular pathways or downstream targets, researchers are now able to carry out in-depth studies of a particular sense, behavior or neural circuit at the molecular level in zebrafish. Importantly, new methods to characterize circuits and cell types, and/or to evaluate deficits in neural function are rapidly growing in number. Historically, behaviors that were amenable to analysis involved simple yet robust reflexes such as startle responses. Although these reflexive behaviors are still important in testing sensory or motor function (Nicolson, 2017; Niklaus & Neuhauss, 2017), other types of behaviors integrating sensory and motor aspects, such as dark avoidance (Wagle, Nguyen, Lee, Zaitlen, & Guo, 2017) and food intake (Allen et al., 2017) are being added to the growing list of quantifiable responses in zebrafish larvae. These developments are facilitating the discovery of novel genes or the generation of new zebrafish models of human neurological diseases.

In this issue, we present reviews of the development and function of the peripheral and central visual system (Niklaus & Neuhauss, 2017; Robles, 2017), including a special focus on cGMP-dependent photoreceptor degeneration (Iribarne & Masai, 2017). We also share updates on the molecular basis of function of two other sensory cell types: acousticolateralis hair cells (Nicolson, 2017), and a novel type of sensor localized in the spinal cord of vertebrates, the cerebrospinal fluid-contacting neuron (Djenoune & Wyart, 2017). Sensory hair cells convert mechanical energy such as sound into electrical signals, and the recent progress on mechanotransduction has led to a working model of the molecular machinery that mediates this process. In contrast to sensory hair cells, the cerebrospinal fluid-contacting neuron is a relative newcomer to the category of sensory cells. Djenoune and Wyart (2017) describe a valuable molecular marker, the transient receptor channel Pkd2l1, that can be used to identify cerebrospinal fluid-contacting neurons and they propose a potential function for these enigmatic cells. In addition, Robles (2017) reviews the recent construction and characterization of the sensory projectomes of the olfactory and optic tracts. Identification of neuronal cell subtypes along with principles of organization and connectivity will be invaluable for understanding how information flows through circuits to be processed in higher brain centers.

In search of alleles associated with anxiety, Wagle et al. (2017) provide evidence of a heritable trait associated with the lack of dark aversion behavior. Identification of anxiety genes and circuitry in fish is a promising avenue for gaining new insights into human psychiatric disorders. Finally, Allen et al. (2017) describe a qualitative but robust feeding assay, and analyze the role of branchiomotor neurons in mediating the intake of food. Ablation of the trigeminal motor neurons or the loss of branchiomotor neurons respectively diminishes or abolishes food intake, indicating that the assay is a sensitive readout of the function of these neurons. This feeding assay can now be exploited to unveil and dissect the circuitry that is vital for feeding.

The zebrafish model combines the ease of applying forward and reverse genetic approaches with the development of behavioral assays such as those highlighted above, along with new imaging and physiological methods. Together, these have contributed to the appeal and success of the zebrafish in addressing fundamental questions in basic neuroscience and in the development of models for neurological diseases. This special issue underscores the central role of the zebrafish model in the ever-widening scope of research into sensory modalities and motor behaviors, and attests to the power of this genetic model system for tackling new areas in cellular and functional neuroscience.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.