Wyatt Korff

Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila

Animals discriminate stimuli, learn their predictive value and use this knowledge to modify their behavior. In Drosophila, the mushroom body (MB) plays a key role in these processes. Sensory stimuli are sparsely represented by ∼2000 Kenyon cells, which converge onto 34 output neurons (MBONs) of 21 types. We studied the role of MBONs in several associative learning tasks and in sleep regulation, revealing the extent to which information flow is segregated into distinct channels and suggesting possible roles for the multi-layered MBON network. We also show that optogenetic activation of MBONs can, depending on cell type, induce repulsion or attraction in flies. The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence. We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli. Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection. DOI: http://dx.doi.org/10.7554/eLife.04580.001

Biomechanics: Deadly strike mechanism of a mantis shrimp

Stomatopods (mantis shrimp) are well known for the feeding appendages they use to smash shells and impale fish. Here we show that the peacock mantis shrimp (Odontodactylus scyllarus) generates an extremely fast strike that requires major energy storage and release, which we explain in terms of a saddle-shaped exoskeletal spring mechanism. High-speed images reveal the formation and collapse of vapour bubbles next to the prey due to swift movement of the appendage towards it, indicating that O. scyllarus may use destructive cavitation forces to damage its prey.

Mapping the Neural Substrates of Behavior

Assigning behavioral functions to neural structures has long been a central goal in neuroscience and is a necessary first step toward a circuit-level understanding of how the brain generates behavior. Here, we map the neural substrates of locomotion and social behaviors for Drosophila melanogaster using automated machine-vision and machine-learning techniques. From videos of 400,000 flies, we quantified the behavioral effects of activating 2,204 genetically targeted populations of neurons. We combined a novel quantification of anatomy with our behavioral analysis to create brain-behavior correlation maps, which are shared as browsable web pages and interactive software. Based on these maps, we generated hypotheses of regions of the brain causally related to sensory processing, locomotor control, courtship, aggression, and sleep. Our maps directly specify genetic tools to target these regions, which we used to identify a small population of neurons with a role in the control of walking.

Environmental differences in substrate mechanics do not affect sprinting performance in sand lizards (Uma scoparia and Callisaurus draconoides)

SUMMARY Running performance depends on a mechanical interaction between the feet of an animal and the substrate. This interaction may differ between two species of sand lizard from the Mojave Desert that have different locomotor morphologies and habitat distributions. Uma scorparia possesses toe fringes and inhabits dunes, whereas the closely related Callisaurus draconoides lacks fringes and is found on dune and wash habitats. The present study evaluated whether these distribution patterns are related to differential locomotor performance on the fine sand of the dunes and the course sand of the wash habitat. We measured the kinematics of sprinting and characterized differences in grain size distribution and surface strength of the soil in both habitats. Although wash sand had a surface strength (15.4±6.2 kPa) that was more than three times that of dune sand (4.7±2.1 kPa), both species ran with similar sprinting performance on the two types of soil. The broadly distributed C. draconoides ran with a slightly (22%) faster maximum speed (2.2±0.2 m s–1) than the dune-dwelling U. scorparia (1.8±0.2 m s–1) on dune sand, but not on wash sand. Furthermore, there were no significant differences in maximum acceleration or the time to attain maximum speed between species or between substrates. These results suggest that differences in habitat distribution between these species are not related to locomotor performance and that sprinting ability is dominated neither by environmental differences in substrate nor the presence of toe fringes.

Principles of appendage design in robots and animals determining terradynamic performance on flowable ground.

Natural substrates like sand, soil, leaf litter and snow vary widely in penetration resistance. To search for principles of appendage design in robots and animals that permit high performance on such flowable ground, we developed a ground control technique by which the penetration resistance of a dry granular substrate could be widely and rapidly varied. The approach was embodied in a device consisting of an air fluidized bed trackway in which a gentle upward flow of air through the granular material resulted in a decreased penetration resistance. As the volumetric air flow, Q, increased to the fluidization transition, the penetration resistance decreased to zero. Using a bio-inspired hexapedal robot as a physical model, we systematically studied how locomotor performance (average forward speed, v(x)) varied with ground penetration resistance and robot leg frequency. Average robot speed decreased with increasing Q, and decreased more rapidly for increasing leg frequency, ω. A universal scaling model revealed that the leg penetration ratio (foot pressure relative to penetration force per unit area per depth and leg length) determined v(x) for all ground penetration resistances and robot leg frequencies. To extend our result to include continuous variation of locomotor foot pressure, we used a resistive force theory based terradynamic approach to perform numerical simulations. The terradynamic model successfully predicted locomotor performance for low resistance granular states. Despite variation in morphology and gait, the performance of running lizards, geckos and crabs on flowable ground was also influenced by the leg penetration ratio. In summary, appendage designs which reduce foot pressure can passively maintain minimal leg penetration ratio as the ground weakens, and consequently permits maintenance of effective locomotion over a range of terradynamically challenging surfaces.

The functional organization of descending sensory-motor pathways in Drosophila

In most animals, the brain controls the body via a set of descending neurons (DNs) that traverse the neck. DN activity activates, maintains or modulates locomotion and other behaviors. Individual DNs have been well-studied in species from insects to primates, but little is known about overall connectivity patterns across the DN population. We systematically investigated DN anatomy in Drosophila melanogaster and created over 100 transgenic lines targeting individual cell types. We identified roughly half of all Drosophila DNs and comprehensively map connectivity between sensory and motor neuropils in the brain and nerve cord, respectively. We find the nerve cord is a layered system of neuropils reflecting the fly’s capability for two largely independent means of locomotion -- walking and flight -- using distinct sets of appendages. Our results reveal the basic functional map of descending pathways in flies and provide tools for systematic interrogation of neural circuits.

Optogenetic dissection of descending behavioral control in Drosophila

In most animals, the brain makes behavioral decisions that are transmitted by descending neurons to the nerve cord circuitry that produces behaviors. In insects, only a few descending neurons have been associated with specific behaviors. To explore how descending neurons control an insect’s movements, we developed a novel method to systematically assay the behavioral effects of activating individual neurons on freely behaving terrestrial D. melanogaster. We calculated a two-dimensional representation of the entire behavior space explored by these flies, and we associated descending neurons with specific behaviors by identifying regions of this space that were visited with increased frequency during optogenetic activation. Applying this approach across a large collection of descending neurons, we found that (1) activation of most of the descending neurons drove stereotyped behaviors, (2) in many cases multiple descending neurons activated similar behaviors, and (3) optogenetically activated behaviors were often dependent on the behavioral state prior to activation.

A Systematic Nomenclature for the Drosophila Ventral Nervous System

Insect nervous systems are proven and powerful model systems for neuroscience research with wide relevance in biology and medicine. However, descriptions of insect brains have suffered from a lack of a complete and uniform nomenclature. Recognising this problem the Insect Brain Name Working Group produced the 1rst agreed hierarchical nomenclature system for the adult insect brain, using Drosophila melanogaster as the reference framework, with other insect taxa considered to ensure greater consistency and expandability (Ito et al., 2014). Ito et al. (2014) purposely focused on the gnathal regions that account for approximately 50% of the adult CNS. We extend this nomenclature system to the sub-gnathal regions of the adult Drosophila nervous system to provide a nomenclature of the so-called ventral nervous system (VNS), which includes the thoracic and abdominal neuromeres that was not included in the original work and contains the neurons that play critical roles underpinning most 2y behaviours.

A screen for constituents of motor control and decision making in Drosophila reveals visual distance-estimation neurons

Climbing over chasms larger than step size is vital to fruit flies, since foraging and mating are achieved while walking. Flies avoid futile climbing attempts by processing parallax-motion vision to estimate gap width. To identify neuronal substrates of climbing control, we screened a large collection of fly lines with temporarily inactivated neuronal populations in a novel high-throughput assay described here. The observed climbing phenotypes were classified; lines in each group are reported. Selected lines were further analysed by high-resolution video cinematography. One striking class of flies attempts to climb chasms of unsurmountable width; expression analysis guided us to C2 optic-lobe interneurons. Inactivation of C2 or the closely related C3 neurons with highly specific intersectional driver lines consistently reproduced hyperactive climbing whereas strong or weak artificial depolarization of C2/C3 neurons strongly or mildly decreased climbing frequency. Contrast-manipulation experiments support our conclusion that C2/C3 neurons are part of the distance-evaluation system.

A single spectrum of neuronal identities across thalamus

A fundamental goal in neuroscience is to uncover common principles by which different modalities of information are processed. In the mammalian brain, thalamus acts as the essential hub for forebrain circuits handling inputs from sensory, motor, limbic, and cognitive pathways. Whether thalamus imposes common transformations on each of these modalities is unknown. Molecular characterization offers a principled approach to revealing the organization of thalamus. Using near-comprehensive and projection-specific transcriptomic sequencing, we found that almost all thalamic nuclei fit into one of three profiles. These profiles lie on a single axis of genetic variance which is aligned with the mediolateral spatial axis of thalamus. Genes defining this axis of variance include receptors and ion channels, providing a systematic diversification of input/output transformations across the topography of thalamus. Single cell transcriptional profiling revealed graded heterogeneity within individual thalamic nuclei, demonstrating that a spectrum of cell types and potentially diverse input/output transforms exist within a given thalamic nucleus. Together, our data argue for an archetypal organization of pathways serving diverse input modalities, and provides a comprehensive organizational scheme for thalamus.Uncovering common principles by which diverse modalities of information are processed is a fundamental goal in neuroscience. In mammalian brain, thalamus is the central processing station for inputs from sensory systems, subcortical motor systems, and cortex; a function subserved by over 30 defined nuclei1,2. Multiple thalamic nuclei send convergent information to each region of the forebrain, but whether there is a conserved architecture across the set of thalamic pathways projecting to each forebrain area has remained unresolved3–5. To uncover organizational principles of thalamic pathways, we produced a near-comprehensive transcriptomic atlas of thalamus. This revealed a common logic for thalamic nuclei serving all major cortical modalities. We found that almost all nuclei belong to one of three major profiles, with a given cortical area getting input from each of these profiles. These profiles lie on a single axis of variance aligned with the mediolateral axis of thalamus, and this axis is strongly enriched in genes encoding receptors and ion channels. We further show that each projection profile exhibits different electrophysiological signatures. Single-cell profiling revealed that rather than forming discrete classes, thalamic neurons lie on a spectrum, with intermediate cells existing between profiles. Thus, in contrast to canonical models of thalamus that suggest it is a switchboard primarily concerned with routing distinct modalities of information to distinct cortical regions, we show that the thalamocortical system is more akin to a molecularly-defined ‘filter bank’ repeatedly applied across modality. Together, we reveal striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensive thalamic functional architecture.Thalamus is the central hub for forebrain communication, a function mediated by approximately 30 nuclei. To uncover organizational principles of the thalamic pathways providing input to the forebrain, we produced a near-comprehensive transcriptomic atlas of its major projection classes. We found that almost all nuclei belong to one of three major profiles that lie on a single axis of variance aligned with the mediolateral axis of thalamus. This axis of variance is strongly enriched in genes encoding receptors and ion channels, and we show that each profile exhibits different electrophysiological signatures. Single-cell profiling revealed even further heterogeneity within established nuclear boundaries, suggesting that the same input to a given nucleus might be differentially processed. Together, our analysis shows striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensive thalamic functional architecture.