Transsynaptic labeling and transcriptional control of zebrafish neural circuits.

Deciphering the connectome, the ensemble of synaptic connections that underlie brain function, is a central goal of neuroscience research. Here we report the in vivo mapping of connections between presynaptic and postsynaptic partners in zebrafish, by adapting the trans-Tango genetic approach that was first developed for anterograde transsynaptic tracing in Drosophila. Neural connections were visualized between synaptic partners in larval retina, brain and spinal cord and followed over development.

A population code for spatial representation in the zebrafish telencephalon.

Spatial learning in teleost fish requires an intact telencephalon, a brain region that contains putative analogues to components of the mammalian limbic system (for example, hippocampus). However, cells fundamental to spatial cognition in mammals-for example, place cells (PCs)-have yet to be established in any fish species. In this study, using tracking microscopy to record brain-wide calcium activity in freely swimming larval zebrafish, we compute the spatial information content of each neuron across the brain.

Simultaneous Behavioral and Neuronal Imaging by Tracking Microscopy.

Tracking microscopy enables whole-brain cellular resolution imaging in freely swimming animals. This technique enables both structural and functional imaging without immobilizing the animal, and greatly expands the range of the behaviors accessible to neuroscientists. We use infrared imaging to track the target animal in a behavioral arena.

Transsynaptic labeling and transcriptional control of zebrafish neural circuits.

Deciphering the connectome, the ensemble of synaptic connections that underlie brain function is a central goal of neuroscience research. The trans-Tango genetic approach, initially developed for anterograde transsynaptic tracing in Drosophila, can be used to map connections between presynaptic and postsynaptic partners and to drive gene expression in target neurons. Here, we describe the successful adaptation of trans-Tango to visualize neural connections in a living vertebrate nervous system, that of the zebrafish.

Emerging principles of spacetime in brains: Meeting report on spatial neurodynamics.

How do neurons and networks of neurons interact spatially? Here, we overview recent discoveries revealing how spatial dynamics of spiking and postsynaptic activity efficiently expose and explain fundamental brain and brainstem mechanisms behind detection, perception, learning, and behavior.

A dynamical systems view of neuroethology: Uncovering stateful computation in natural behaviors.

State-dependent computation is key to cognition in both biological and artificial systems. Alan Turing recognized the power of stateful computation when he created the Turing machine with theoretically infinite computational capacity in 1936. Independently, by 1950, ethologists such as Tinbergen and Lorenz also began to implicitly embed rudimentary forms of state-dependent computation to create qualitative models of internal drives and naturally occurring animal behaviors.

Regional synapse gain and loss accompany memory formation in larval zebrafish.

Defining the structural and functional changes in the nervous system underlying learning and memory represents a major challenge for modern neuroscience. Although changes in neuronal activity following memory formation have been studied [B. F.

Cerebellar Neurodynamics Predict Decision Timing and Outcome on the Single-Trial Level.

Goal-directed behavior requires the interaction of multiple brain regions. How these regions and their interactions with brain-wide activity drive action selection is less understood. We have investigated this question by combining whole-brain volumetric calcium imaging using light-field microscopy and an operant-conditioning task in larval zebrafish.

Internal state dynamics shape brainwide activity and foraging behaviour.

The brain has persistent internal states that can modulate every aspect of an animal's mental experience. In complex tasks such as foraging, the internal state is dynamic. Caenorhabditis elegans alternate between local search and global dispersal.

Epi-illumination gradient light interference microscopy for imaging opaque structures.

Multiple scattering and absorption limit the depth at which biological tissues can be imaged with light. In thick unlabeled specimens, multiple scattering randomizes the phase of the field and absorption attenuates light that travels long optical paths. These obstacles limit the performance of transmission imaging.

A Brain-wide Circuit Model of Heat-Evoked Swimming Behavior in Larval Zebrafish.

Thermosensation provides crucial information, but how temperature representation is transformed from sensation to behavior is poorly understood. Here, we report a preparation that allows control of heat delivery to zebrafish larvae while monitoring motor output and imaging whole-brain calcium signals, thereby uncovering algorithmic and computational rules that couple dynamics of heat modulation, neural activity and swimming behavior. This approach identifies a critical step in the transformation of temperature representation between the sensory trigeminal ganglia and the hindbrain: A simple sustained trigeminal stimulus representation is transformed into a representation of absolute temperature as well as temperature changes in the hindbrain that explains the observed motor output.

Gaze-Stabilizing Central Vestibular Neurons Project Asymmetrically to Extraocular Motoneuron Pools.

Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations, such as asymmetric connectivity, to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish.

Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish.

Calcium imaging with cellular resolution typically requires an animal to be tethered under a microscope, which substantially restricts the range of behaviors that can be studied. To expand the behavioral repertoire amenable to imaging, we have developed a tracking microscope that enables whole-brain calcium imaging with cellular resolution in freely swimming larval zebrafish. This microscope uses infrared imaging to track a target animal in a behavior arena.

The structure and timescales of heat perception in larval zebrafish.

Avoiding temperatures outside the physiological range is critical for animal survival, but how temperature dynamics are transformed into behavioral output is largely not understood. Here, we used an infrared laser to challenge freely swimming larval zebrafish with "white-noise" heat stimuli and built quantitative models relating external sensory information and internal state to behavioral output. These models revealed that larval zebrafish integrate temperature information over a time-window of 400 ms preceding a swimbout and that swimming is suppressed right after the end of a bout.

A convergent and essential interneuron pathway for Mauthner-cell-mediated escapes.

The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3].

Whole-brain functional imaging at cellular resolution using light-sheet microscopy.

Brain function relies on communication between large populations of neurons across multiple brain areas, a full understanding of which would require knowledge of the time-varying activity of all neurons in the central nervous system. Here we use light-sheet microscopy to record activity, reported through the genetically encoded calcium indicator GCaMP5G, from the entire volume of the brain of the larval zebrafish in vivo at 0.8 Hz, capturing more than 80% of all neurons at single-cell resolution.

The tangential nucleus controls a gravito-inertial vestibulo-ocular reflex.

Background: Although adult vertebrates sense changes in head position by using two classes of accelerometer, at larval stages zebrafish lack functional semicircular canals and rely exclusively on their otolithic organs to transduce vestibular information.

Results: Despite this limitation, we find that larval zebrafish perform an effective vestibulo-ocular reflex (VOR) that serves to stabilize gaze in response to pitch and roll tilts. By using single-cell electroporations and targeted laser ablations, we identified a specific class of central vestibular neurons, located in the tangential nucleus, that are essential for the utricle-dependent VOR.

Brain-wide neuronal dynamics during motor adaptation in zebrafish.

A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites.

Somatic stem cell niche tropism in Wolbachia.

Wolbachia are intracellular bacteria found in the reproductive tissue of all major groups of arthropods. They are transmitted vertically from the female hosts to their offspring, in a pattern analogous to mitochondria inheritance. But Wolbachia phylogeny does not parallel that of the host, indicating that horizontal infectious transmission must also occur.

Discovery of biological networks from diverse functional genomic data.

We have developed a general probabilistic system for query-based discovery of pathway-specific networks through integration of diverse genome-wide data. This framework was validated by accurately recovering known networks for 31 biological processes in Saccharomyces cerevisiae and experimentally verifying predictions for the process of chromosomal segregation. Our system, bioPIXIE, a public, comprehensive system for integration, analysis, and visualization of biological network predictions for S.