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Randel, N.

Publications and source records attributed to Randel, N..

7 recordsLinked to original sources

The female larval fly CNS connectome: first draft

We release an enhanced FIB-SEM volume and associated neuron, mitochondria, synapse and glia automated segmentations for the complete, gap- and artifact-free central nervous system of the first instar female larval Drosophila melanogaster. Segmentation data is largely unproofread besides select neurons in the premotor and proprioceptive system and select subvolumes where synapses have been manually annotated, serving as training and evaluation data. The dataset represents the first complete central nervous system of the larval fly, and now awaits substantial improvement of machine vision approaches that effectively leverage domain knowledge for the automated yet data-guided proofreading, or substantial and costly human proofreading. All the data and methods are publicly available for further improvement and analysis.

neuroscience↗

Combining brainwide activity imaging and electron microscopy reveals novel nociceptive circuits

To understand how brains work, it is necessary to connect neural activity to synaptic-resolution circuit architecture. Recent advances in light-sheet microscopy (LSM) enable whole-brain, cellular-resolution imaging of activity of all neuronal cell bodies, however, most neurons from such datasets cannot be identified. In most organisms, neurons are identifiable based on their projections (and not based on their cell body position) which, when densely labelled, cannot be resolved using LSM. Here, we present a novel methodology to overcome this by combining whole-brain activity imaging with subsequent volume electron microscopy imaging of the same brain to visualise neuronal projections and identify neurons with interesting activity. We used this approach to identify brain neurons that process input from multisensory (nociceptive and mechanosensory) Basin interneurons that trigger vigorous escape in Drosophila larvae in response to threatening somatosensory stimuli. After whole-brain imaging of neuronal activity during Basin activation, we imaged the same brain with an enhanced focused ion-beam electron microscope (eFIB-SEM). We registered the functional and anatomical volumes and reconstructed (in the eFIB-SEM volume) the projections of neurons that responded to Basin activation to determine their developmental lineage and identity. This revealed a distributed network for processing threatening somatosensory stimuli that trigger vigorous escape spanning 25 distinct lineages and many distinct brain areas, and included direct brain targets of Basin neurons that integrate somatosensory information with other modalities, as well as brain output neurons (descending neurons [DN]) that likely contribute to action-selection. Our workflow provides a powerful framework for mapping neuronal activity onto structure across an entire brain, yielding novel insights into the distributed central processing of noxious stimuli.

neuroscience↗

Cross-species comparative connectomics reveals the evolution of an olfactory circuit

Animal behavioural diversity ultimately stems from variation in neural circuitry, yet how central neural circuits evolve remains poorly understood. Studies of neural circuit evolution often focus on a few elements within a network. However, addressing fundamental questions in evolutionary neuroscience, such as whether some elements are more evolvable than others, requires a more global and unbiased approach. Here, we used synapse-level comparative connectomics to examine how an entire olfactory circuit evolves. We compared the full antennal lobe connectome of the larvae of two closely related Drosophila species, D. melanogaster and D. erecta, which differ in their ecological niches and odour-driven behaviours. We found that evolutionary change is unevenly distributed across the network. Some features, including neuron types, neuron numbers and interneuron-to-interneuron connectivity, are highly conserved. These conserved elements delineate a core circuit blueprint presumably required for fundamental olfactory processing. Superimposed on this scaffold, we find rewiring changes that mirror each species ecologies, including a systematic shift in the excitation-to-inhibition balance in the feedforward pathways. We further show that some neurons have changed more than others, and that even within individual neurons some synaptic elements remain conserved while others display major species-specific changes, suggesting evolutionary hot-spots within the circuit. Our findings reveal constrained and adaptable elements within olfactory networks, and establish a framework for identifying general principles in the evolution of neural circuits underlying behaviour.

neuroscience↗

Effects of food availability on larval development during ontogenetic niche shift in a marine annelid

Many marine invertebrates have a biphasic life cycle with a free-swimming larva and a bottom-dwelling adult. The transition from a planktonic to a benthic lifestyle is a significant step in the animals life history, highly regulated and influenced by external and internal factors. Since the readiness to settle and the presence of a suitable seafloor habitat do not always coincide, larvae sometimes need to extend their planktonic phase. Little is currently known regarding how larvae partition their energy for coordinating development and growth according to food type and availability in their settlement habitat. Here, I investigate the effect of food availability and type on development in Platynereis dumerilii larvae. I assessed cell proliferation, growth, and feeding onset over six days using two different food sources. The results indicate that food availability and type affect larval growth, with starved larvae slowing development and conserving resources, whereas fed larvae allocate resources to brain development and posterior growth. Overall, this work contributes to our understanding of how competent marine larvae regulate the duration of their planktonic phase and how nutritional status affects development.

ecology↗

The connectome of an insect brain

Brains contain networks of interconnected neurons, so knowing the network architecture is essential for understanding brain function. We therefore mapped the synaptic-resolution connectome of an insect brain (Drosophila larva) with rich behavior, including learning, value-computation, and action-selection, comprising 3,013 neurons and 544,000 synapses. We characterized neuron-types, hubs, feedforward and feedback pathways, and cross-hemisphere and brain-nerve cord interactions. We found pervasive multisensory and interhemispheric integration, highly recurrent architecture, abundant feedback from descending neurons, and multiple novel circuit motifs. The brains most recurrent circuits comprised the input and output neurons of the learning center. Some structural features, including multilayer shortcuts and nested recurrent loops, resembled powerful machine learning architectures. The identified brain architecture provides a basis for future experimental and theoretical studies of neural circuits. One-Sentence SummaryWe generated a synaptic-resolution brain connectome and characterized its connection types, neuron types, and circuit motifs.

neuroscience↗

BigStitcher: Reconstructing high-resolution image datasets of cleared and expanded samples

New methods for clearing and expansion of biological objects create large, transparent samples that can be rapidly imaged using light-sheet microscopy. Resulting image acquisitions are terabytes in size and consist of many large, unaligned image tiles that suffer from optical distortions. We developed the BigStitcher software that efficiently handles and reconstructs large multi-tile, multi-view acquisitions compensating all major optical effects, thereby making single-cell resolved whole-organ datasets amenable to biological studies.

bioinformatics↗

Ciliary and rhabdomeric photoreceptor-cell circuits form a spectral depth gauge in marine zooplankton

Ciliary and rhabdomeric photoreceptor cells represent two main lines of photoreceptor evolution in animals. The two photoreceptor-cell types coexist in some animals, however how they functionally integrate is unknown. We used connectomics to map synaptic paths between ciliary and rhabdomeric photoreceptors in the planktonic larva of the annelid Platynereis and found that ciliary photoreceptors are presynaptic to the rhabdomeric circuit. The behaviors mediated by the ciliary and rhabdomeric cells also interact hierarchically. The ciliary photoreceptors are UV-sensitive and mediate downward swimming to non-directional UV light, a behavior absent in ciliary-opsin knockouts. UV avoidance antagonizes positive phototaxis mediated by the rhabdomeric eyes so that vertical swimming direction is determined by the ratio of blue/UV light. Since this ratio increases with depth, Platynereis larvae may use it as a depth gauge during planktonic migration. Our results revealed a functional integration of ciliary and rhabdomeric photoreceptors with implications for eye and photoreceptor evolution.

neuroscience↗