Katja Slangewal

Animals continuously extract and evaluate diverse sensory information from the environment to guide behavior. Yet, how neural circuits integrate multiple, potentially conflicting, inputs remains poorly understood. Here, we use larval zebrafish to address this question, leveraging their robust optomotor response to coherent random dot motion and phototaxis towards light. We demonstrate that animals employ an additive behavioral algorithm of three visual features: motion coherence, luminance level, and changes in luminance. Using brain-wide two-photon imaging, we identify the loci of these computations, with the anterior hindbrain emerging as a multifeature integration hub. Through single-cell neurotransmitter and morphological analyses of functionally identified neurons, we characterize potential connections within and across computational nodes. These experiments reveal three parallel and converging computational pathways, matching our behavioral results. Our study provides a mechanistic brain-wide account of how a vertebrate brain integrates multiple features to drive sensorimotor decisions, bridging behavioral algorithms with their neural implementation.

RNA ligases are essential for the repair, splicing, and editing of RNA across various biological systems. Recently, a new enzyme that catalyses 5’-3’ RNA ligation – RNA ligase 1 (Rlig1) – was identified in vitro . However, the in vivo biological functions of Rlig1 have remained elusive. Here, we reveal the role of Rlig1 during vertebrate development using embryonic and larval zebrafish as a model system. We found that rlig1 mRNA is maternally deposited and present ubiquitously during early embryogenesis, whereas at larval stages it localises to the brain and eyes. Interestingly, CRISPR/Cas9-generated rlig1 knockout zebrafish exhibited no overt morphological abnormalities, but showed reduced behavioural responsiveness to visual stimuli along with massively perturbed transcriptomes and widespread dysregulation of core metabolic and translational pathways. Brain-wide calcium imaging in rlig1 knockout larvae revealed decreased neuronal activity in key regions for visual processing, consistent with the observed behavioural defects. Together, our findings identify a role for Rlig1 in maintaining the integrity and function of the nervous system and uncover a new link between neuronal RNA processing, development, and sensory-motor computation.

SUMMARY: Animals continuously extract and evaluate diverse sensory information from the environment to guide behavior. Yet, how neural circuits integrate multiple, potentially conflicting, inputs during decision-making remains poorly understood. Here, we use larval zebrafish to address this question, leveraging their robust optomotor response to coherent random dot motion and phototaxis towards light. We demonstrate that animals employ an additive behavioral algorithm of three visual features: motion coherence, luminance level, and changes in luminance. Using brain-wide two-photon imaging, we identify the loci of these computations, with the anterior hindbrain emerging as a multifeature sensory integration hub. Through single-cell neurotransmitter and morphological analyses of functionally identified neurons, we characterize potential connections within and across computational nodes. These experiments reveal three parallel and converging pathways, matching our behavioral results. Our study provides a mechanistic brain-wide account of how a vertebrate brain integrates multiple features to drive sensorimotor decisions, bridging the algorithmic bases of behavior and its neural implementation.

SUMMARY: Animals undergo major behavioral adjustments during ontogeny, but how the underlying cognitive algorithms change during this process remains elusive. Here, we describe that zebrafish shift from light-seeking to dark-seeking, as they grow from larval to juvenile stage, within the first few weeks of their life. We apply a combination of complementary phototaxis assays in virtual reality and modeling to dissect the computational basis of this transition. We identify three parallel pathways, one analyzing ambient whole-field luminance levels, one spatially comparing light levels across the eyes, and one computing eye-specific temporal derivatives. Larvae mostly use the latter two spatio-temporal computations for navigation, while juveniles largely employ the first one. We build a library of agent-based models to predict animal behavior across stimulation conditions and in more complex environments. Model-based extraction of latent cognitive variables points towards potential neural correlates of the observed behavioral inversion and illustrates a novel way to explore the processes of vertebrate ontogeny. We suggest that zebrafish phototaxis is regulated via parallel processing streams, which could be a universal implementation to change strategies depending on developmental stage, context, or internal state, making behavior flexible and goal-oriented. GRAPHICAL HIGHLIGHTS: We provide a framework to describe how behavioral strategies evolve during ontogeny. Zebrafish switch their phototactic behavior within the first weeks of their life. Brightness navigation strategies can be described with a three-pathway model. Larvae use spatial cues, while juveniles use ambient whole-field luminance for phototaxis.

Our interaction with the surrounding environment shapes how our brain processes sensory information and drives adaptive behaviour. This plasticity allows the brain to rewire in response to specific sensory experiences. For instance, early manipulation of visual inputs profoundly impacts brain plasticity, which is crucial for functions like size perception, object recognition, and visuospatial processing. While neuronal plasticity has been detected in visual target structures such as the colliculus, thalamus, and cortex, it remains unclear if the retina, the primary sensory organ, undergoes significant plasticity. Here, we show that the zebrafish retina demonstrates pronounced plastic transformations in response to alterations of the visual environment during development, which ultimately modifies the detection of oriented visual stimuli. We demonstrate that orientation-selective amacrine cells undergo profound morphological changes in animals exposed to distinct visual environments during development. We further find that the functional orientation-selective output from the retina is altered in a manner consistent with the visual environment in which the animals are raised and that these changes are persistent. Finally, animals tested in a virtual reality system show that early exposure to different visual environments changes their innate preference for specifically oriented patterns. Our findings unveil a unique developmental form of sensory organ plasticity with continuing structural and functional consequences.

To integrate noisy visual motion, vertebrate circuits must transform transient sensory signals into persistent, lateralized activity. The synaptic architecture supporting this computation remains unclear. We combined calcium imaging and correlative electron microscopy (EM) in larval zebrafish with an independent whole-brain EM dataset, reconstructing 1,246 neurons in and connected to the anterior hindbrain, a region previously implicated in the temporal integration of visual evidence. We identified four broad functional and morphological classes interconnected through recurrent excitation, interhemispheric and ipsilateral inhibitory motifs, as well as long-range inputs from rostral visual regions. We then trained bilateral neural networks constrained by the measured neuron-to-neuron connectivity as a fixed anatomical mask, while optimizing unknown physiological weights. These models reproduced population dynamics and predicted responses to previously untested motion stimuli. Shuffling connectivity or selectively removing recurrent connections impaired model performance, whereas removing an equivalent number of random connections across the network had much smaller effects. Our results identify an anatomical network compatible with visual-motion integration and implicate specific recurrent connections in its computational dynamics. Together, our results link functional dynamics with synaptic architecture in a vertebrate sensorimotor circuit and provide a framework for interpreting connectomic datasets through combined functional, anatomical, and computational analyses.

Social affiliation emerges from individual-level behavioural rules that are driven by conspecific signals^1–5. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred interanimal distance in swarms^6–8. However, little is known about their perceptual mechanisms and executive neural circuits³. Here we trace the neuronal response to self-like biological motion^9,10, a visual trigger for affiliation in developing zebrafish^2,11. Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 21 activity hotspots distributed throughout the brain as well as clustered biological-motion-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus. Individual dorsal thalamus neurons encode local acceleration of visual stimuli mimicking typical fish kinetics but are insensitive to global or continuous motion. Electron microscopic reconstruction of dorsal thalamus neurons revealed synaptic input from the optic tectum and projections into hypothalamic areas with conserved social function^12–14. Ablation of the optic tectum or dorsal thalamus selectively disrupted social attraction without affecting short-distance repulsion. This tectothalamic pathway thus serves visual recognition of conspecifics, and dissociates neuronal control of attraction from repulsion during social affiliation, revealing a circuit underpinning collective behaviour.

Social affiliation emerges from individual-level behavioral rules that are driven by conspecific signals ^1–5 . Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred inter-animal distance in swarms ^6–8 . However, little is known about their perceptual mechanisms and executive neuronal circuits ³ . Here we trace the neuronal response to self-like biological motion ^9,10 (BM), a visual trigger for affiliation in developing zebrafish ^2,11 . Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 19 activity hotspots distributed throughout the brain and clustered BM-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus (DT). Individual DT neurons encode fish-like local acceleration but are insensitive to global or continuous motion. Electron microscopic reconstruction of DT neurons revealed synaptic input from the optic tectum (TeO/superior colliculus) and projections into nodes of the conserved social behavior network ^12,13 . Chemogenetic ablation of the TeO selectively disrupted DT responses to BM and social attraction without affecting short-distance repulsion. Together, we discovered a tecto-thalamic pathway that drives a core network for social affiliation. Our findings provide an example of visual social processing, and dissociate neuronal control of attraction from repulsion during affiliation, thus revealing neural underpinnings of collective behavior.