secCl is a cys-loop ion channel necessary for the chloride conductance that mediates hormone-induced fluid secretion in Drosophila

Organisms use circulating diuretic hormones to control water balance (osmolarity), thereby avoiding dehydration and managing excretion of waste products. The hormones act through G-protein-coupled receptors to activate second messenger systems that in turn control the permeability of secretory epithelia to ions like chloride. In insects, the chloride channel mediating the effects of diuretic hormones was unknown. Surprisingly, we find a pentameric, cys-loop chloride channel, a type of channel normally associated with neurotransmission, mediating hormone-induced transepithelial chloride conductance. This discovery is important because: 1) it describes an unexpected role for pentameric receptors in the membrane permeability of secretory epithelial cells, and 2) it suggests that neurotransmitter-gated ion channels may have evolved from channels involved in secretion

Motor context dominates output from purkinje cell functional regions during reflexive visuomotor behaviours

The cerebellum integrates sensory stimuli and motor actions to enable smooth coordination and motor learning. Here we harness the innate behavioral repertoire of the larval zebrafish to characterize the spatiotemporal dynamics of feature coding across the entire Purkinje cell population during visual stimuli and the reflexive behaviors that they elicit. Population imaging reveals three spatially-clustered regions of Purkinje cell activity along the rostrocaudal axis. Complementary single-cell electrophysiological recordings assign these Purkinje cells to one of three functional phenotypes that encode a specific visual, and not motor, signal via complex spikes. In contrast, simple spike output of most Purkinje cells is strongly driven by motor-related tail and eye signals. Interactions between complex and simple spikes show heterogeneous modulation patterns across different Purkinje cells, which become temporally restricted during swimming episodes. Our findings reveal how sensorimotor information is encoded by individual Purkinje cells and organized into behavioral modules across the entire cerebellum

Whole-Brain Imaging Using Genetically Encoded Activity Sensors in Vertebrates

In the mid-twentieth century, the development of electrophysiology revolutionized the way that the brain could be studied, allowing scientists to advance beyond anatomy and neuroethology and address questions involving brain function. These recordings offered a temporally and spatially high-resolution readout of the activity of single cells and enabled a detailed understanding of the input–output function of individual neurons. Nevertheless, understanding the brain one neuron at a time seems like a daunting task. Over the last two decades, a considerable amount of research has focused on understanding the brain at the mesoscale of brain circuits and networks, trying to bridge the gap from single neurons to the function of the whole brain in generating behavior. This is a large, open and exciting field that encompasses theory, computational models, behavioral studies, genetic manipulations and many more approaches. Importantly, the current interest in brain circuits is fueled by the development of new techniques that allow us to acquire data relevant to addressing network function and the activity of large populations of neurons. In this chapter, we present an introduction to whole-brain, single-cell resolution imaging in a behaving vertebrate model organism, the larval zebrafish. We describe the fundamental concepts developed during the last five years that are important for understanding large-scale imaging techniques in vertebrates from experimental design to data acquisition and analysis

Sensorimotor representations in cerebellar granule cells in larval zebrafish are dense, spatially organized, and non-temporally patterned

A fundamental question in neurobiology is how animals integrate external sensory information from their environment with self-generated motor and sensory signals in order to guide motor behavior and adaptation. The cerebellum is a vertebrate hind-brain region where all of these signals converge and that has been implicated in the acquisition, coordination, and calibration of motor activity. Theories of cerebellar function postulate that granule cells encode a variety of sensorimotor signals in the cerebellar input layer. These models suggest that representations should be high-dimensional, sparse, and temporally patterned. However, in vivo physiological recordings addressing these points have been limited and in particular have been unable to measure the spatiotemporal dynamics of population-wide activity. In this study, we use both calcium imaging and electrophysiology in the awake larval zebrafish to investigate how cerebellar granule cells encode three types of sensory stimuli as well as stimulus-evoked motor behaviors. We find that a large fraction of all granule cells are active in response to these stimuli, such that representations are not sparse at the population level. We find instead that most responses belong to only one of a small number of distinct activity profiles, which are temporally homogeneous and anatomically clustered. We furthermore identify granule cells that are active during swimming behaviors and others that are multimodal for sensory and motor variables. When we pharmacologically change the threshold of a stimulus-evoked behavior, we observe correlated changes in these representations. Finally, electrophysiological data show no evidence for temporal patterning in the coding of different stimulus durations