Biology subjects

Dombrovski, M.

Publications and source records attributed to Dombrovski, M..

5 recordsLinked to original sources

bioRxiv2025

Electrical synapses mediate visual approach behavior

Detecting salient visual objects and orienting toward them are commonplace tasks for animals, yet the underlying neural circuits remain poorly understood. The fruit fly is an ideal model for a comprehensive analysis of feature detection mechanisms given its complete synaptic wiring diagrams, robust behavioral assays, and cell-type-specific gene expression datasets. We previously showed that columnar T3 neurons are required for saccadic orientation toward landscape features during flight. Here, we examine how signals downstream of T3 are processed in the central brain. We identify LC17 visual projection neurons as key postsynaptic targets: they receive strong excitatory input from T3, project to premotor brain regions, and are thus positioned to support visual approach. Using in vivo optical physiology and virtual reality behavior, we demonstrate that LC17 neurons are indeed necessary for object tracking during flight. Furthermore, we find that electrical synapses in LC17 are also required for tracking behavior. We show that the innexin Shaking B (shakB) is highly expressed in LC17 and localized to its dendrites, and genetic perturbations confirm its essential role for electrical coupling in this circuit. Our findings reveal mechanisms underlying visual approach, and highlight the interplay between electrical and chemical neurotransmission for rapid object detection and action selection.

neuroscience↗

bioRxiv2024

Gradients of Recognition Molecules Shape Synaptic Specificity of a Visuomotor Transformation

Converting sensory information into motor commands is fundamental to most of our actions. In Drosophila, visuomotor transformations are mediated by Visual Projection Neurons (VPNs). These neurons convert object location and motion into directional behaviors downstream through a synaptic gradient mechanism. However, the molecular origins of such graded connectivity remain unknown. We addressed this question in a VPN cell type called LPLC2, which integrates looming motion and transforms it into an escape response through two parallel dorsoventral synaptic gradients at its inputs and outputs. We identified two corresponding dorsoventral expression gradients of cell recognition molecules within the LPLC2 population that regulate this synaptic connectivity. Dpr13 determines synaptic outputs of LPLC2 axons by interacting with its binding partner DIP-{varepsilon} expressed in the Giant Fiber, a neuron that mediates escape. Similarly, beat-VI regulates synaptic inputs onto LPLC2 dendrites by interacting with Side-II expressed in upstream motion-detecting neurons. Behavioral, physiological, and molecular experiments demonstrate that these coordinated molecular gradients control differential synaptic connectivity, enabling the accurate transformation of visual features into motor commands. As within-neuronal-type variation in gene expression is also observed in the mammalian brain, graded expression of cell recognition molecules may represent a common mechanism underlying synaptic specificity.

neuroscience↗

bioRxiv2024

Neuronal identity control at the resolution of a single transcription factor isoform

The brain exhibits remarkable neuronal diversity which is critical for its functional integrity. From the sheer number of cell types emerging from extensive transcriptional, morphological, and connectome datasets, the question arises of how the brain is capable of generating so many unique identities. Terminal selectors are transcription factors hypothesized to determine the final identity characteristics in post-mitotic cells. Which transcription factors function as terminal selectors and the level of control they exert over different terminal characteristics are not well defined. Here, we establish a novel role for the transcription factor broad as a terminal selector in Drosophila melanogaster. We capitalize on existing large sequencing and connectomics datasets and employ a comprehensive characterization of terminal characteristics including Perturb-seq and whole-cell electrophysiology. We find a single isoform broad-z4 serves as the switch between the identity of two visual projection neurons LPLC1 and LPLC2. Broad-z4 is natively expressed in LPLC1, and is capable of transforming the transcriptome, morphology, and functional connectivity of LPLC2 cells into LPLC1 cells when perturbed. Our comprehensive work establishes a single isoform as the smallest unit underlying an identity switch, which may serve as a conserved strategy replicated across developmental programs.

neuroscience↗

bioRxiv2023

Identifying determinants of synaptic specificity by integrating connectomes and transcriptomes

How do developing neurons select their synaptic partners? To identify molecules matching synaptic partners, we integrated the synapse-level connectome of neural circuits with the developmental expression patterns and binding specificities of cell adhesion molecules (CAMs) on pre- and postsynaptic neurons. We focused on parallel synaptic pathways in the Drosophila visual system, in which closely related neurons form synapses onto closely related target neurons. We show that the choice of synaptic partners correlates with the matching expression of receptor-ligand pairs of Beat and Side proteins of the immunoglobulin superfamily (IgSF) CAMs. Genetic analysis demonstrates that these proteins determine the choice between alternative synaptic targets. Combining transcriptomes, connectomes, and protein interactome maps provides a framework to uncover the molecular logic of synaptic connectivity.

neuroscience↗

bioRxiv2020

Cooperative foraging during larval stage affects fitness in Drosophila

Cooperative behavior can confer advantages to animals. This is especially true for cooperative foraging which provides fitness benefits through more efficient acquisition and consumption of food. While examples of group foraging have been widely described, the principles governing formation of such aggregations and rules that determine group membership remain poorly understood. Here we take advantage of an experimental model system featuring cooperative foraging behavior in Drosophila. Under crowded conditions, fly larvae form coordinated digging groups (clusters), where individuals are linked together by sensory cues and group membership requires prior experience. However, fitness benefits of Drosophila larval clustering remain unknown. We demonstrate that animals raised in crowded conditions on food partially processed by other larvae experience a developmental delay presumably due to the decreased nutritional value of the substrate. Intriguingly, same conditions promote formation of cooperative foraging clusters which further extends larval stage compared to non-clustering animals. Remarkably, this developmental retardation also results in a relative increase in wing size, serving an indicator of adult fitness. Thus, we find that the clustering-induced developmental delay is accompanied by fitness benefits. Therefore, cooperative foraging, while delaying development, may have evolved to give Drosophila larvae benefits when presented with competition for limited food resources.

animal behavior and cognition↗