Biology subjects

Larsch, J.

Publications and source records attributed to Larsch, J..

5 recordsLinked to original sources

bioRxiv2024

Positional information drives distinct traits in transcriptomically identified neuronal types

Neuronal phenotypic traits such as morphology, connectivity, and function are dictated, to a large extent, by a specific combination of differentially expressed genes. Clusters of neurons in transcriptomic space correspond to distinct cell types and in some cases (e. g., C. elegans neurons1 and retinal ganglion cells2-4) have been shown to share morphology and function. The zebrafish optic tectum is composed of a spatial array of neurons that transforms visual inputs into motor outputs. While the visuotopic map is continuous, subregions of the tectum are functionally specialized5,6. To uncover the cell-type architecture of the tectum, we transcriptionally profiled its neurons, revealing more than 60 cell types that are organized in distinct anatomical layers. We then measured the visual responses of thousands of tectal neurons by two-photon calcium imaging and matched them with their transcriptional profile. Furthermore, we characterized the morphologies of transcriptionally identified neurons using specific transgenic lines. Surprisingly, we found that neurons that are transcriptionally similar can diverge functionally and morphologically. Incorporating the spatial coordinates of neurons within the tectal volume revealed functionally and morphologically defined anatomical subclusters within individual transcriptomic clusters. Our findings demonstrate that extrinsic, position-dependent factors expand the phenotypic repertoire of genetically similar neurons.

neuroscience↗

bioRxiv2022

A single-cell resolution gene expression atlas of the larval zebrafish brain

The advent of multimodal brain atlases promises to accelerate discoveries in neuroscience by offering in silico queries of cell types, connectivity and gene expression in regions of interest. We employed multiplexed fluorescent in situ RNA hybridization chain reaction (HCR) to generate expression maps for an initial set of 200 marker genes across the larval zebrafish brain. The data were registered to the Max Planck Zebrafish Brain (mapzebrain) atlas, thus allowing co-visualization of gene expression patterns, single-neuron tracings, transgenic lines and anatomical segmentations. Additionally, brain activity maps of freely swimming larvae were generated at single-cell resolution using HCR labeling of the immediate-early gene cfos and integrated into the atlas. As a proof of concept, we identified a novel class of cerebellar eurydendroid cells that express calb2a, project to the hypothalamus and are activated in animals that have recently ingested food. Thus, a cellular-resolution gene expression atlas will not only help with rapid identification of marker genes for neuronal populations of interest, but also bridge the molecular and circuit levels by anchoring genetic information to functional activity maps and synaptic connectivity.

neuroscience↗

bioRxiv2021

Visual recognition of social signals by a tecto-thalamic neural circuit

Social affiliation emerges from individual-level behavioral rules that are driven by conspecific signals1-5. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred inter-animal distance in swarms6-8. However, little is known about their perceptual mechanisms and executive neuronal circuits3. Here we trace the neuronal response to self-like biological motion9,10 (BM), a visual trigger for affiliation in developing zebrafish2,11. 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 network12,13. 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.

neuroscience↗

bioRxiv2019

Neuronal circuitry for stimulus selection in the visual system

Visual objects naturally compete for the brains attention, and selecting just one of them for a behavioural response is often crucial for the animals survival1. The neural correlate of such stimulus prioritisation might take the form of a saliency map by which responses to one target are enhanced relative to distractors in other parts of the visual field2. Single-cell responses consistent with this type of computation have been observed in the tectum of primates, birds, turtles and lamprey2-7. However, the exact circuit implementation has remained unclear. Here we investigated the underlying neuronal mechanism presenting larval zebrafish with two simultaneous looming stimuli, each of which was able to trigger directed escapes on their own. Behaviour tracking revealed that the fish respond to these competing stimuli predominantly with a winner-take-all strategy. Using brain-wide functional recordings, we discovered neurons in the tectum whose responses to the target stimulus were non-linearly modulated by the saliency of the distractor. When the two stimuli were presented monocularly in different positions of the visual field, stimulus selection was already apparent in the activity of retinal ganglion cell axons, a likely consequence of antagonistic mechanisms operating outside the classical receptive field8,9. When the two stimuli were presented binocularly, i.e., on opposite sides of the fish, our analysis indicates that a loop involving excitatory and inhibitory neurons in the nucleus isthmi (NI) and the tectum weighed stimulus saliencies across hemispheres. Consistent with focal enhancement and global suppression, glutamatergic NI cells branch locally in the tectum, whereas GABAergic NI cells project broadly across both tectal hemispheres. Moreover, holographic optogenetic stimulation confirmed that glutamatergic NI neurons can modulate visual responses in the tectum. Together, our study shows, for the first time, context-dependent contributions of retinotectal and isthmotectal circuits to the computation of the visual saliency map, a prerequisite for stimulus-driven, bottom-up attention.

neuroscience↗

bioRxiv2018

Biological motion as an innate perceptual mechanism driving social affiliation

Collective behavior, such as shoaling in teleost fish, is driven by the perceptual recognition of conspecific animals. Because social interactions are mutual, it has been difficult to disentangle the exact sensory cues that trigger affiliation in the first place from those that are emitted by receptive and responsive shoal mates. Here we overcome this challenge in a virtual reality assay in zebrafish. We discovered that simple visual features of conspecific biological motion provide an irresistible shoaling cue. Individual juvenile fish interact with circular black dots projected onto a screen, to the same extent as they do with real conspecifics, provided these virtual objects mimic the characteristic kinetics of zebrafish swim bouts. Other naturalistic cues previously implicated in shoaling, such as fish-like shape, pigmentation pattern, or non-visual sensory modalities are not required. During growth, the animals stimulus preferences shift gradually, matching self-like kinetics, even in fish raised in isolation. Virtual group interactions and our multi-agent model implementation of this perceptual mechanism demonstrate sufficiency of kinetic cues to drive assortative shoaling, a phenomenon commonly observed in field studies. Coordinated behavior can emerge from autonomous interactions, such as collective odor avoidance in Drosophila, or from reciprocal interactions, such as the codified turn-taking in wren duet singing. We found that individual zebrafish shoal autonomously without evidence for a reciprocal choreography. Our results reveal individual-level, innate perceptual rules of engagement in mutual affiliation and provide experimental access to the neural mechanisms of social recognition. (239/250 words max)\n\nSignificance StatementSocial affiliation is ubiquitous in the animal kingdom, but fundamental sensory cues driving group formation remain elusive. During swarm behavior, for example, individuals dynamically exchange sensory cues with their neighbors, presenting an intertwined choreography opaque to formal analysis of causal stimulus-response relationships. Using a virtual interaction assay for psychophysical analysis, we solved this issue and identify biological motion as the irresistible trigger of social affiliation in zebrafish, Danio rerio. Given that many species form groups including shoals, flocks and herds, perceptual mechanisms of social recognition and their underlying neural circuits are likely shared across vertebrates. The identification of fundamental affiliation-inducing cues is a prerequisite for relating individual-level sensory-motor transformations to collective behavior. (112/120 words max)

neuroscience↗