Biology subjects

Sancer, G.

Publications and source records attributed to Sancer, G..

7 recordsLinked to original sources

bioRxiv2025

Sensory processing reformats odor coding around valence and dynamics

Extracting relevant features of a complex sensory signal typically involves sequential processing through multiple brain regions. However, identifying the logic and mechanisms of these transformations has been difficult, due to the challenges of measuring both activity within and long-range connectivity between multiple neural populations. Here, we investigate the reformatting of odor information across two stages of the Drosophila olfactory system. We measure the odor tuning of 20 types of anatomically-defined third order lateral horn neuron (LHN) and compare to predictions based on the odor tuning of second-order projection neurons (PNs) and PN-LHN connectivity. We find that LHNs reformat PN activity in two distinct ways. First, LHNs selectively discard information about odor identities with similar valence (i.e., attractiveness or aversiveness). This emerges from a precise alignment of PN odor tuning and PN-LHN connectivity, as well as odor-specific inhibition and boosting of LHN activity. This creates a population code for valence that is more explicit than in PNs. Second, a subset of LHNs selectively discard information about continuing odor presence, by responding only transiently to odor onset. This creates a population code for odor dynamics that is more explicit than in PNs. Across LHNs, valence and dynamics are independent of each other. Thus, feedforward connectivity and local inhibition combine to extract two orthogonal dimensions of olfactory information.

neuroscience↗

bioRxiv2023

Connectomic reconstruction predicts the functional organization of visual inputs to the navigation center of the Drosophila brain

Many animals, including humans, navigate their surroundings by visual input, yet we understand little about how visual information is transformed and integrated by the navigation system. In Drosophila melanogaster, compass neurons in the donut-shaped ellipsoid body of the central complex generate a sense of direction by integrating visual input from ring neurons, a part of the anterior visual pathway (AVP). Here, we densely reconstruct all neurons in the AVP using FlyWire, an AI-assisted tool for analyzing electron-microscopy data. The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons, which connect the medulla in the optic lobe to the small unit of anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons, which connect the anterior optic tubercle to the bulb neuropil; and ring neurons, which connect the bulb to the ellipsoid body. Based on neuronal morphologies, connectivity between different neural classes, and the locations of synapses, we identified non-overlapping channels originating from four types of MeTu neurons, which we further divided into ten subtypes based on the presynaptic connections in medulla and postsynaptic connections in AOTUsu. To gain an objective measure of the natural variation within the pathway, we quantified the differences between anterior visual pathways from both hemispheres and between two electron-microscopy datasets. Furthermore, we infer potential visual features and the visual area from which any given ring neuron receives input by combining the connectivity of the entire AVP, the MeTu neurons dendritic fields, and presynaptic connectivity in the optic lobes. These results provide a strong foundation for understanding how distinct visual features are extracted and transformed across multiple processing stages to provide critical information for computing the flys sense of direction.

neuroscience↗

bioRxiv2023

Neuronal "parts list" and wiring diagram for a visual system

A catalog of neuronal cell types has often been called a "parts list" of the brain, and regarded as a prerequisite for understanding brain function. In the optic lobe of Drosophila, rules of connectivity between cell types have already proven essential for understanding fly vision. Here we analyze the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. We more than double the list of known types. Most new cell types contain between 10 and 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi) at least double in number of types. We introduce a new Sm interneuron family, which contains more types than any other, and three new families of cross-neuropil types. Self-consistency of cell types is demonstrated through automatic assignment of cells to types by distance in high-dimensional feature space, and further validation is provided by algorithms that select small subsets of discriminative features. Cell types with similar connectivity patterns divide into clusters that are interpretable in terms of motion, object, and color vision. Our work showcases the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity, and reduction of the connectome to a drastically simpler wiring diagram of cell types, with immediate relevance for brain function and development.

neuroscience↗

bioRxiv2021

Synaptic targets of functionally specialized R7 and R8 photoreceptors in the central eye and dorsal rim area of Drosophila

Color and polarization provide complementary information about the world and are detected by specialized photoreceptors. However, the downstream neural circuits that process these distinct modalities are incompletely understood in any animal. Using electron microscopy, we have systematically reconstructed the synaptic targets of the photoreceptors specialized to detect color and skylight polarization in Drosophila, and we have used light microscopy to confirm many of our findings. We identified known and novel downstream targets that are selective for different wavelengths or polarized light, and followed their projections to other areas in the optic lobes and the central brain. Our results revealed many synapses along the photoreceptor axons between brain regions, new pathways in the optic lobes, and spatially segregated projections to central brain regions. Strikingly, photoreceptors in the polarization-sensitive dorsal rim area target fewer cell types, and lack strong connections to the lobula, a neuropil involved in color processing. Our reconstruction identifies shared wiring and modality-specific specializations for color and polarization vision, and provides a comprehensive view of the first steps of the pathways processing color and polarized light inputs.

neuroscience↗

bioRxiv2020

Parallel visual pathways with topographic versus non-topographic organization connect the Drosophila eyes to the central brain

One hallmark of the visual system is the strict retinotopic organization from the periphery towards the central brain, spanning multiple layers of synaptic integration. Recent Drosophila studies on the computation of distinct visual features have shown that retinotopic representation is often lost beyond the optic lobes, due to convergence of columnar neuron types onto optic glomeruli. Nevertheless, functional imaging revealed a spatially accurate representation of visual cues in the central complex (CX), raising the question how this is implemented on a circuit level. By characterizing the afferents to a specific visual glomerulus, the anterior optic tubercle (AOTU), we discovered a spatial segregation of topographic versus non-topographic projections from molecularly distinct classes of medulla projection neurons (medullo-tubercular, or MeTu neurons). Distinct classes of topographic versus non-topographic MeTus form parallel channels, terminating in separate AOTU domains. Both types then synapse onto separate matching topographic fields of tubercular-bulbar (TuBu) neurons which relay visual information towards the dendritic fields of central complex ring neurons in the bulb neuropil, where distinct bulb sectors correspond to a distinct ring domain in the ellipsoid body. Hence, peripheral topography is maintained due to stereotypic circuitry within each TuBu class, providing the structural basis for spatial representation of visual information in the central complex. Together with previous data showing rough topography of lobula projections to a different AOTU subunit, our results further highlight the AOTUs role as a prominent relay station for spatial information from the retina to the central brain.

neuroscience↗

bioRxiv2019

Cellular and synaptic adaptations of neural circuits processing skylight polarization in the fly

Specialized ommatidia harboring polarization-sensitive photoreceptors exist in the dorsal rim area (DRA) of virtually all insects. Although downstream elements have been described both anatomically and physiologically throughout the optic lobes and the central brain of different species, little is known about their cellular and synaptic adaptations and how these shape their functional role in polarization vision. We have previously shown that in the DRA of Drosophila melanogaster, two distinct types of modality-specific distal medulla cell types (Dm-DRA1 and Dm-DRA2) are post-synaptic to long visual fiber photoreceptors R7 and R8, respectively. Here we describe additional neuronal elements in the medulla neuropil that manifest modality-specific differences in the DRA region, including DRA-specific neuronal morphology, as well as differences in the structure of pre- or post-synaptic membranes. Furthermore, we show that certain cell types (medulla tangential cells and octopaminergic neuromodulatory cells) specifically avoid contacts with polarization-sensitive photoreceptors. Finally, while certain transmedullary cells are specifically absent from DRA medulla columns, other subtypes show specific wiring differences while still connecting the DRA to the lobula complex, as previously been described in larger insects. This hints towards a complex circuit architecture with more than one pathway connecting polarization-sensitive DRA photoreceptors with the central brain.

neuroscience↗

bioRxiv2019

Modality-specific circuits for skylight orientation in the fly visual system

In the fly optic lobe [~]800 highly stereotypical columnar microcircuits are arranged retinotopically to process visual information. Differences in cellular composition and synaptic connectivity within functionally specialized columns remains largely unknown. Here we describe the cellular and synaptic architecture in medulla columns located downstream of photoreceptors in the dorsal rim area (DRA), where linearly polarized skylight is detected for guiding orientation responses. We show that only in DRA medulla columns, both R7 and R8 photoreceptors target to the bona fide R7 target layer where they form connections with previously uncharacterized, modality-specific Dm neurons: Two morphologically distinct DRA-specific cell types (termed Dm-DRA1 and Dm-DRA2) stratify in separate sublayers and exclusively contact polarization-sensitive DRA inputs, while avoiding overlaps with color-sensitive Dm8 cells. Using the activity-dependent GRASP and trans-Tango techniques, we confirm that DRA R7 cells are synaptically connected to Dm-DRA1, whereas DRA R8 form synapses with Dm-DRA2. Finally, using live imaging of ingrowing pupal photoreceptor axons, we show that DRA R7 and R8 termini reach layer M6 sequentially, thus separating the establishment of different synaptic connectivity in time. We propose that a duplication of R7[->]Dm circuitry in DRA ommatidia serves as an ideal adaptation for detecting linearly polarized skylight using orthogonal e-vector analyzers.

neuroscience↗