Biology subjects

Engert, F.

Publications and source records attributed to Engert, F..

48 records · Page 3Linked to original sources

bioRxiv2020

Social isolation modulates appetite and defensive behavior via a common oxytocinergic circuit in larval zebrafish

Animal brains have evolved to encode social stimuli and transform these representations into advantageous behavioral responses. The commonalities and differences of these representations across species are not well-understood. Here, we show that social isolation activates an oxytocinergic (OXT), nociceptive circuit in the larval zebrafish hypothalamus and that chemical cues released from conspecific animals are potent modulators of this circuits activity. We delineate an olfactory to subpallial pathway that transmits chemical social cues to OXT circuitry, where they are transformed into diverse outputs simultaneously regulating defensive and feeding behaviors. Our data allow us to propose a model through which social stimuli are integrated within a fundamental neural circuit to mediate diverse adaptive behaviours.

neuroscience↗

bioRxiv2019

Cerebellar neurodynamics during motor planning predict decision timing and outcome on single-trial level

The neuronal basis of goal-directed behavior requires interaction of multiple separated brain regions. How subcortical regions and their interactions with brain-wide activity are involved in action selection is less understood. We have investigated this question by developing an assay based on whole-brain volumetric calcium imaging using light-field microscopy combined with an operant-conditioning task in larval zebrafish. We find global and recurring dynamics of brain states to exhibit pre-motor bifurcations towards mutually exclusive decision outcomes which arises from a spatially distributed network. Within this network the cerebellum shows a particularly strong pre-motor activity, predictive of both the timing and outcome of behavior up to [~]10 seconds before movement initiation. Furthermore, on the single-trial level, decision directions can be inferred from the difference neuroactivity between the ipsilateral and contralateral hemispheres, while the decision time can be quantitatively predicted by the rate of bi-hemispheric population ramping activity. Our results point towards a cognitive role of the cerebellum and its importance in motor planning.

neuroscience↗

bioRxiv2019

Elements of a stochastic 3D prediction engine in larval zebrafish prey capture

Many predatory animals rely on accurate sensory perception, predictive models, and precise pursuits to catch moving prey. Larval zebrafish intercept paramecia during their hunting behavior, but the precise trajectories of their prey have never been recorded in relation to fish movements in three dimensions.\n\nAs a means of uncovering what a simple organism understands about its physical world, we have constructed a 3D-imaging setup to simultaneously record the behavior of larval zebrafish, as well as their moving prey, during hunting. We show that zebrafish robustly transform their 3D displacement and rotation according to the position of their prey while modulating both of these variables depending on prey velocity. This is true for both azimuth and altitude, but particulars of the hunting algorithm in the two planes are slightly different to accommodate an asymmetric strike zone. We show that the combination of position and velocity perception provides the fish with a preferred future positional estimate, indicating an ability to project trajectories forward in time. Using computational models, we show that this projection ability is critical for prey capture efficiency and success. Further, we demonstrate that fish use a graded stochasticity algorithm where the variance around the mean result of each swim scales with distance from the target. Notably, this strategy provides the animal with a considerable improvement over equivalent noise-free strategies.\n\nIn sum, our quantitative and probabilistic modeling shows that zebrafish are equipped with a stochastic recursive algorithm that embodies an implicit predictive model of the world. This algorithm, built by a simple set of behavioral rules, allows the fish to optimize their hunting strategy in a naturalistic three-dimensional environment.

animal behavior and cognition↗

bioRxiv2019

Probabilistic Models of Larval Zebrafish Behavior: Structure on Many Scales

Nervous systems have evolved to combine environmental information with internal state to select and generate adaptive behavioral sequences. To better understand these computations and their implementation in neural circuits, natural behavior must be carefully measured and quantified. Here, we collect high spatial resolution video of single zebrafish larvae swimming in a naturalistic environment and develop models of their action selection across exploration and hunting. Zebrafish larvae swim in punctuated bouts separated by longer periods of rest called interbout intervals. We take advantage of this structure by categorizing bouts into discrete types and representing their behavior as labeled sequences of bout-types emitted over time. We then construct probabilistic models - specifically, marked renewal processes - to evaluate how bout-types and interbout intervals are selected by the fish as a function of its internal hunger state, behavioral history, and the locations and properties of nearby prey. Finally, we evaluate the models by their predictive likelihood and their ability to generate realistic trajectories of virtual fish swimming through simulated environments. Our simulations capture multiple timescales of structure in larval zebrafish behavior and expose many ways in which hunger state influences their action selection to promote food seeking during hunger and safety during satiety.

animal behavior and cognition↗

bioRxiv2019

A bidirectional network for appetite control in zebrafish

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

neuroscience↗

bioRxiv2018

Distributed plasticity drives visual habituation learning in larval zebrafish

Habituation is a simple form of learning, where animals learn to reduce their responses to repeated innocuous stimuli. While habituation is simple in concept, its exact implementation in the vertebrate brain is not clear. It could occur via a single plasticity event at a singular site in the circuit, or alternatively via more complex strategies that combine multiple mechanisms at various processing stages and sites. Here, we use a visual habituation assay in larval zebrafish, where larvae habituate to sudden reductions in illumination (dark flashes). We find that 8 different components of this response habituate, including the probability of executing a response, its latency, and measures of its magnitude. Through behavioural analyses, we find that habituation of these different behavioural components occurs independently of each other and at different locations in the circuit. Further, we use genetic and pharmacological manipulations to show that habituation of different behavioural components are molecularly distinct. These results are consistent with a model by which visual habituation originates from the combination of multiple independent processes, which each act to adapt specific components of behaviour. This may allow animals to more specifically habituate behaviour based on stimulus context or internal state.

neuroscience↗

bioRxiv2018

Convergent temperature representations in artificial and biological neural networks

While discoveries in biological neural networks (BNN) shaped artificial neural networks (ANN) it is unclear if representations and algorithms are shared between ANNs and BNNs performing similar tasks. Here, we designed and trained an ANN to perform heat gradient navigation and found striking similarities in computation and heat representation to a known zebrafish BNN. This included shared ON and OFF type representations of absolute temperature and rates of change. Importantly, ANN function critically relied on zebrafish like units. We could furthermore use the accessibility of the ANN to discover a new temperature responsive cell type in the zebrafish cerebellum. Finally, our approach generalized since training the same ANN constrained by the C. elegans motor repertoire resulted in distinct neural representations matching features observed in the worm. Together, these results emphasize convergence of ANNs and BNNs on canonical representations and that ANNs form a powerful tool to understand their biological counterparts.

neuroscience↗

bioRxiv2018

Brainwide organization of neuronal activity and convergent sensorimotor transformations in larval zebrafish

Simultaneous recordings of large populations of neurons in behaving animals allow detailed observation of high-dimensional, complex brain activity. However, experimental design and analysis approaches have not sufficiently evolved to fully realize the potential of these methods. We recorded whole-brain neuronal activity for larval zebrafish presented with a battery of visual stimuli while recording fictive motor output. These data were used to develop analysis methods including regression techniques that leverage trial-to-trial variations and unsupervised clustering techniques that organize neurons into functional groups. We used these methods to obtain brain-wide maps of concerted activity, which revealed both known and heretofore uncharacterized brain nuclei. We also identified neurons tuned to each stimulus type and motor output, and revealed nuclei in the anterior hindbrain that respond to multiple stimuli that elicit the same behavior. However, these convergent sensorimotor representations were only weakly correlated to instantaneous motor behavior, suggesting that they inform, but do not directly generate, behavioral output. These findings motivate a novel model of sensorimotor transformation spanning distinct behavioral contexts, within which these hindbrain convergence neurons likely constitute a key step.

neuroscience↗

bioRxiv2017

A brain wide circuit model of heat evoked swimming behavior in larval zebrafish

Thermosensation provides crucial information but it is poorly understood how temperature representation is transformed from sensation to behavior. 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. An activity constrained dynamic circuit model captures the most prominent aspects of these sensori-motor transformations and predicts both behavior and neural activity in response to novel heat stimuli. These findings provide the first algorithmic description of heat processing from sensory input to behavioral output.

neuroscience↗

bioRxiv2017

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. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concor-dantly, when the entire population of asymmetrically-projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically-projecting central population thus participates in both up and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially-projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze-stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically-relevant stimuli without compromising reflexive behavior.\n\nSignificance StatementInterneuron populations use specific anatomical projections to transform sensations into reflexive actions. Here we examined how the anatomical composition of a genetically-defined population of balance interneurons in the larval zebrafish relates to the computations it performs. First, we found that the population of interneurons that stabilize gaze preferentially project to motoneurons that move the eyes downward. Next, we discovered through modeling that such projection patterns can enhance the encoding of nose-up sensations without compromising gaze stabilization. Finally we found that loss of these interneurons impairs a vital behavior, swim bladder inflation, that relies on maintaining a nose-up posture. These observations suggest that anatomical specialization permits neural circuits to represent relevant features of the environment without compromising behavior.

neuroscience↗

bioRxiv2017

Lamellar Junctions In The Endolymphatic Sac Act As A Relief Valve To Regulate Inner Ear Pressure

The inner ear is a fluid-filled closed-epithelial structure whose normal function requires maintenance of an internal hydrostatic pressure and fluid composition by unknown mechanisms. The endolymphatic sac (ES) is a dead-end epithelial tube connected to the inner ear. ES defects can cause distended ear tissue, a pathology often seen in hearing and balance disorders. Using live imaging of zebrafish larvae, we reveal that the ES undergoes cycles of slow pressure-driven inflation followed by rapid deflation every 1-3 hours. Using serial-section electron microscopy and adaptive optics lattice light-sheet microscopy, we find a pressure relief valve in the ES comprised of thin overlapping basal lamellae that dynamically extend over neighboring cells before rupturing under pressure leading to ES collapse. The unexpected discovery of a physical relief valve in the ear emphasizes the need for further study into how organs control fluid pressure, volume, flow, and ion homeostasis in development and disease.

developmental biology↗

bioRxiv2017

Whole-Brain Serial-Section Electron Microscopy In Larval Zebrafish

Investigating the dense meshwork of wires and synapses that form neuronal circuits is possible with the high resolution of serial-section electron microscopy (ssEM)1. However, the imaging scale required to comprehensively reconstruct axons and dendrites is more than 10 orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons2--some of which span nearly the entire brain. The difficulties in generating and handling data for relatively large volumes at nanoscale resolution has thus restricted all studies in vertebrates to neuron fragments, thereby hindering investigations of complete circuits. These efforts were transformed by recent advances in computing, sample handling, and imaging techniques1, but examining entire brains at high resolution remains a challenge. Here we present ssEM data for a complete 5.5 days post-fertilisation larval zebrafish brain. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management. The resulting dataset can be analysed to reconstruct neuronal processes, allowing us to, for example, survey all the myelinated axons (the projectome). Further, our reconstructions enabled us to investigate the precise projections of neurons and their contralateral counterparts. In particular, we observed that myelinated axons of reticulospinal and lateral line afferent neurons exhibit remarkable bilateral symmetry. Additionally, we found that fasciculated reticulospinal axons maintain the same neighbour relations throughout the extent of their projections. Furthermore, we use the dataset to set the stage for whole-brain comparisons of structure and function by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. We provide the complete dataset and reconstructions as an open-access resource for neurobiologists and others interested in the ultrastructure of the larval zebrafish.

neuroscience↗