Synaptic gradients transform object location to action.

To survive, animals must convert sensory information into appropriate behaviours1,2. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses3-5. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs)6,7 into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly's directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

A population of descending neurons that regulates the flight motor of Drosophila.

Similar to many insect species, Drosophila melanogaster is capable of maintaining a stable flight trajectory for periods lasting up to several hours.1,2 Because aerodynamic torque is roughly proportional to the fifth power of wing length,3 even small asymmetries in wing size require the maintenance of subtle bilateral differences in flapping motion to maintain a stable path. Flies can even fly straight after losing half of a wing, a feat they accomplish via very large, sustained kinematic changes to both the damaged and intact wings.4 Thus, the neural network responsible for stable flight must be capable of sustaining fine-scaled control over wing motion across a large dynamic range. In this study, we describe an unusual type of descending neuron (DNg02) that projects directly from visual output regions of the brain to the dorsal flight neuropil of the ventral nerve cord. Unlike many descending neurons, which exist as single bilateral pairs with unique morphology, there is a population of at least 15 DNg02 cell pairs with nearly identical shape. By optogenetically activating different numbers of DNg02 cells, we demonstrate that these neurons regulate wingbeat amplitude over a wide dynamic range via a population code. Using two-photon functional imaging, we show that DNg02 cells are responsive to visual motion during flight in a manner that would make them well suited to continuously regulate bilateral changes in wing kinematics. Collectively, we have identified a critical set of descending neurons that provides the sensitivity and dynamic range required for flight control.

Data-driven statistical modeling of the emergent behavior of biohybrid microrobots.

Multi-agent biohybrid microrobotic systems, owing to their small size and distributed nature, offer powerful solutions to challenges in biomedicine, bioremediation, and biosensing. Synthetic biology enables programmed emergent behaviors in the biotic component of biohybrid machines, expounding vast potential benefits for building biohybrid swarms with sophisticated control schemes. The design of synthetic genetic circuits tailored toward specific performance characteristics is an iterative process that relies on experimental characterization of spatially homogeneous engineered cell suspensions. However, biohybrid systems often distribute heterogeneously in complex environments, which will alter circuit performance. Thus, there is a critically unmet need for simple predictive models that describe emergent behaviors of biohybrid systems to inform synthetic gene circuit design. Here, we report a data-driven statistical model for computationally efficient recapitulation of the motility dynamics of two types of Escherichia coli bacteria-based biohybrid swarms-NanoBEADS and BacteriaBots. The statistical model was coupled with a computational model of cooperative gene expression, known as quorum sensing (QS). We determined differences in timescales for programmed emergent behavior in BacteriaBots and NanoBEADS swarms, using bacteria as a comparative baseline. We show that agent localization and genetic circuit sensitivity strongly influence the timeframe and the robustness of the emergent behavior in both systems. Finally, we use our model to design a QS-based decentralized control scheme wherein agents make independent decisions based on their interaction with other agents and the local environment. We show that synergistic integration of synthetic biology and predictive modeling is requisite for the efficient development of biohybrid systems with robust emergent behaviors.

Integrating nanofibers with biochemical gradients to investigate physiologically-relevant fibroblast chemotaxis.

Persistent cell migration can occur due to anisotropy in the extracellular matrix (ECM), the gradient of a chemo-effector, or a combination of both. Through a variety of in vitro platforms, the contributions of either stimulus have been extensively studied, while the combined effect of both cues remains poorly described. Here, we report an integrative microfluidic chemotaxis assay device that enables the study of single cell chemotaxis on ECM-mimicking, aligned, and suspended nanofibers. Using this assay, we evaluated the effect of fiber spacing on the morphology and chemotaxis response of embryonic murine NIH/3T3 fibroblasts in the presence of temporally invariant, linear gradients of platelet-derived growth factor-BB (PDGF-BB). We found that the strength of PDGF-mediated chemotaxis response depends on not only the gradient slope but also the cell morphology. Low aspect ratio (3.4 ± 0.2) cells on flat substrata exhibited a chemotaxis response only at a PDGF-BB gradient of 0-10 ng mL-1. However, high aspect ratio (19.1 ± 0.7) spindle-shaped cells attached to individual fibers exhibited maximal chemotaxis response at a ten-fold shallower gradient of 0-1 ng mL-1, which was robustly maintained up to 0-10 ng mL-1. Quadrilateral-shaped cells of intermediate aspect ratio (13.6 ± 0.8) attached to two fibers exhibited a weaker response compared to the spindle-shaped cells, but still stronger compared to cells attached to 2D featureless substrata. Through pharmacological inhibition, we show that the mesenchymal chemotaxis pathway is conserved in cells on fibers. Altogether, our findings show that chemotaxis on ECM-mimicking fibers is modulated by fiber spacing-driven cell shape and can be significantly different from the behavior observed on flat 2D substrata. We envisage that this microfluidic platform will have wide applicability in understanding the combined role of ECM architecture and chemotaxis in physiological and pathological processes.