Paired and solitary ionocytes in the zebrafish olfactory epithelium.

The sense of smell is generated by electrical currents that are influenced by the concentration of ions in olfactory sensory neurons and mucus. In contrast to the extensive morphological and molecular characterization of sensory neurons, there has been little description of the cells that control ion concentrations in the zebrafish olfactory system. Here, we report the molecular and ultrastructural characterization of zebrafish olfactory ionocytes.

Kalium channelrhodopsins effectively inhibit neurons.

The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)-recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect.

Computational modeling of light processing in the habenula and dorsal raphe based on laser ablation of functionally-defined cells.

Background: The habenula is a major regulator of serotonergic neurons in the dorsal raphe, and thus of brain state. The functional connectivity between these regions is incompletely characterized. Here, we use the ability of changes in irradiance to trigger reproducible changes in activity in the habenula and dorsal raphe of zebrafish larvae, combined with two-photon laser ablation of specific neurons, to establish causal relationships.

Glial cells expressing visual cycle genes are vital for photoreceptor survival in the zebrafish pineal gland.

Photoreceptors in the vertebrate eye are dependent on the retinal pigmented epithelium for a variety of functions including retinal re-isomerization and waste disposal. The light-sensitive pineal gland of fish, birds, and amphibians is evolutionarily related to the eye but lacks a pigmented epithelium. Thus, it is unclear how these functions are performed.

Dynamics and potential significance of spontaneous activity in the habenula.

The habenula is an evolutionarily conserved structure of the vertebrate brain that is essential for behavioural flexibility and mood control. It is spontaneously active and is able to access diverse states when the animal is exposed to sensory stimuli. Here we investigate the dynamics of habenula spontaneous activity, to gain insight into how sensitivity is optimized.

The habenula clock influences response to a stressor.

The response of an animal to a sensory stimulus depends on the nature of the stimulus and on expectations, which are mediated by spontaneous activity. Here, we ask how circadian variation in the expectation of danger, and thus the response to a potential threat, is controlled. We focus on the habenula, a mediator of threat response that functions by regulating neuromodulator release, and use zebrafish as the experimental system.

Olfactory Rod Cells: A Rare Cell Type in the Larval Zebrafish Olfactory Epithelium With a Large Actin-Rich Apical Projection.

We report the presence of a rare cell type, the olfactory rod cell, in the developing zebrafish olfactory epithelium. These cells each bear a single actin-rich rod-like apical projection extending 5-10 μm from the epithelial surface. Live imaging with a ubiquitous Lifeact-RFP label indicates that the olfactory rods can oscillate.

Neural correlates of state transitions elicited by a chemosensory danger cue.

Background: Detection of predator cues changes the brain state in prey species and helps them avoid danger. Dysfunctionality in changing the central state appropriately in stressful situations is proposed to be an underlying cause of multiple psychiatric disorders in humans.

Methods: Here, we investigate the dynamics of neural circuits mediating response to a threat, to characterize these states and to identify potential control networks.

Identification of GABAergic neurons innervating the zebrafish lateral habenula.

Habenula neurons are constantly active. The level of activity affects mood and behaviour, with increased activity in the lateral habenula reflecting exposure to punishment and a switch to passive coping and depression. Here, we identify GABAergic neurons that could reduce activity in the lateral habenula of larval zebrafish.

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly.

The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution. Here, we show that the mitochondrial proteome, particularly the respiratory chain, is enriched for small proteins. Using a prediction and validation pipeline for SEPs, we report the discovery of 16 endogenous nuclear encoded, mitochondrial-localized SEPs (mito-SEPs).

Bacteria evoke alarm behaviour in zebrafish.

When injured, fish release an alarm substance (Schreckstoff) that elicits fear in members of their shoal. Although Schreckstoff has been proposed to be produced by club cells in the skin, several observations indicate that these giant cells function primarily in immunity. Previous data indicate that the alarm substance can be isolated from mucus.

Characterization of a thalamic nucleus mediating habenula responses to changes in ambient illumination.

Background: Neural activity in the vertebrate habenula is affected by ambient illumination. The nucleus that links photoreceptor activity with the habenula is not well characterized. Here, we describe the location, inputs and potential function of this nucleus in larval zebrafish.

Optical inhibition of larval zebrafish behaviour with anion channelrhodopsins.

Background: Optical silencing of activity provides a way to test the necessity of neurons in behaviour. Two light-gated anion channels, GtACR1 and GtACR2, have recently been shown to potently inhibit activity in cultured mammalian neurons and in Drosophila. Here, we test the usefulness of these channels in larval zebrafish, using spontaneous coiling behaviour as the assay.

The thalamo-habenula projection revisited.

The thalamus is one of the most highly connected hubs of the vertebrate brain, with roles in perception, arousal, navigation, memory and consciousness. One connection that is missing from contemporary maps is a link to the habenula. This link was reported in the early part of the last century, but appears to have slipped into obscurity.

Masking of a circadian behavior in larval zebrafish involves the thalamo-habenula pathway.

Changes in illumination can rapidly influence behavior that is normally controlled by the circadian clock. This effect is termed masking. In mice, masking requires melanopsin-expressing retinal ganglion cells that detect blue light and project to the thalamus.

Loss of the Habenula Intrinsic Neuromodulator Kisspeptin1 Affects Learning in Larval Zebrafish.

Learning how to actively avoid a predictable threat involves two steps: recognizing the cue that predicts upcoming punishment and learning a behavioral response that will lead to avoidance. In zebrafish, ventral habenula (vHb) neurons have been proposed to participate in both steps by encoding the expected aversiveness of a stimulus. vHb neurons increase their firing rate as expectation of punishment grows but reduce their activity as avoidance learning occurs.

Imaging voltage in zebrafish as a route to characterizing a vertebrate functional connectome: promises and pitfalls of genetically encoded indicators.

Neural circuits are non-linear dynamical systems that transform information based on the pattern of input, current state and functional connectivity. To understand how a given stimulus is processed, one would ideally record neural activity across the entire brain of a behaving animal, at cellular or even subcellular resolution, in addition to characterizing anatomical connectivity. Given their transparency and relatively small size, larval zebrafish provide a powerful system for brain-wide monitoring of neural activity.

Activation and inhibition of tph2 serotonergic neurons operate in tandem to influence larval zebrafish preference for light over darkness.

Serotonergic neurons have been implicated in a broad range of processes, but the principles underlying their effects remain a puzzle. Here, we ask how these neurons influence the tendency of larval zebrafish to swim in the light and avoid regions of darkness. Pharmacological inhibition of serotonin synthesis reduces dark avoidance, indicating an involvement of this neuromodulator.

The right dorsal habenula limits attraction to an odor in zebrafish.

Background: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays.

Zebrafish forebrain and temporal conditioning.

The rise of zebrafish as a neuroscience research model organism, in conjunction with recent progress in single-cell resolution whole-brain imaging of larval zebrafish, opens a new window of opportunity for research on interval timing. In this article, we review zebrafish neuroanatomy and neuromodulatory systems, with particular focus on identifying homologies between the zebrafish forebrain and the mammalian forebrain. The neuroanatomical and neurochemical basis of interval timing is summarized with emphasis on the potential of using zebrafish to reveal the neural circuits for interval timing.

Tactile stimulation reduces fear in fish.

Being groomed or touched can counter stress and negative affect in mammals. In two experiments we explored whether a similar phenomenon exists in non-mammals like zebrafish. In Experiment 1, we exposed zebrafish to a natural stressor, a chemical alarm signal released by injured conspecifics.

A microfluidic device to sort cells based on dynamic response to a stimulus.

Single cell techniques permit the analysis of cellular properties that are obscured by studying the average behavior of cell populations. One way to determine how gene expression contributes to phenotypic differences among cells is to combine functional analysis with transcriptional profiling of single cells. Here we describe a microfluidic device for monitoring the responses of single cells to a ligand and then collecting cells of interest for transcriptional profiling or other assays.