@article {48507, title = {Angular velocity integration in a fly heading circuit.}, journal = {eLife}, volume = {6}, year = {2017}, month = {2017 May 22}, abstract = {

Many animals maintain an internal representation of their heading as they move through their surroundings. Such a compass representation was recently discovered in a neural population in the Drosophila melanogaster central complex, a brain region implicated in spatial navigation. Here, we use two-photon calcium imaging and electrophysiology in head-fixed walking flies to identify a different neural population that conjunctively encodes heading and angular velocity, and is excited selectively by turns in either the clockwise or counterclockwise direction. We show how these mirror-symmetric turn responses combine with the neurons{\textquoteright} connectivity to the compass neurons to create an elegant mechanism for updating the fly{\textquoteright}s heading representation when the animal turns in darkness. This mechanism, which employs recurrent loops with an angular shift, bears a resemblance to those proposed in theoretical models for rodent head direction cells. Our results provide a striking example of structure matching function for a broadly relevant computation.

}, issn = {2050-084X}, doi = {10.7554/eLife.23496}, author = {Turner-Evans, Daniel and Wegener, Stephanie and Rouault, Herv{\'e} and Franconville, Romain and Wolff, Tanya and Seelig, Johannes D and Druckmann, Shaul and Jayaraman, Vivek} } @article {48304, title = {Video-rate volumetric functional imaging of the brain at synaptic resolution.}, journal = {Nature Neuroscience}, volume = {20}, year = {2017}, month = {2017 Feb 27}, pages = {620-8}, abstract = {

Neurons and neural networks often extend hundreds of micrometers in three dimensions. Capturing the calcium transients associated with their activity requires volume imaging methods with subsecond temporal resolution. Such speed is a challenge for conventional two-photon laser-scanning microscopy, because it depends on serial focal scanning in 3D and indicators with limited brightness. Here we present an optical module that is easily integrated into standard two-photon laser-scanning microscopes to generate an axially elongated Bessel focus, which when scanned in 2D turns frame rate into volume rate. We demonstrated the power of this approach in enabling discoveries for neurobiology by imaging the calcium dynamics of volumes of neurons and synapses in fruit flies, zebrafish larvae, mice and ferrets in vivo. Calcium signals in objects as small as dendritic spines could be resolved at video rates, provided that the samples were sparsely labeled to limit overlap in their axially projected images.

}, issn = {1546-1726}, doi = {10.1038/nn.4516}, author = {Lu, Rongwen and Sun, Wenzhi and Liang, Yajie and Kerlin, Aaron and Bierfeld, Jens and Seelig, Johannes D and Wilson, Daniel E and Scholl, Benjamin and Mohar, Boaz and Tanimoto, Masashi and Koyama, Minoru and Fitzpatrick, David and Orger, Michael B and Ji, Na} } @article {46694, title = {Neural dynamics for landmark orientation and angular path integration.}, journal = {Nature}, volume = {521}, year = {2015}, month = {2015 May 14}, pages = {186-191}, abstract = {

Many animals navigate using a combination of visual landmarks and path integration. In mammalian brains, head direction cells integrate these two streams of information by representing an animal{\textquoteright}s heading relative to landmarks, yet maintaining their directional tuning in darkness based on self-motion cues. Here we use two-photon calcium imaging in head-fixed Drosophila melanogaster walking on a ball in a virtual reality arena to demonstrate that landmark-based orientation and angular path integration are combined in the population responses of neurons whose dendrites tile the ellipsoid body, a toroidal structure in the centre of the fly brain. The neural population encodes the fly{\textquoteright}s azimuth relative to its environment, tracking visual landmarks when available and relying on self-motion cues in darkness. When both visual and self-motion cues are absent, a representation of the animal{\textquoteright}s orientation is maintained in this network through persistent activity, a potential substrate for short-term memory. Several features of the population dynamics of these neurons and their circular anatomical arrangement are suggestive of ring attractors, network structures that have been proposed to support the function of navigational brain circuits.

}, doi = {10.1038/nature14446}, author = {Seelig, Johannes D and Jayaraman, Vivek} } @article {6481, title = {Feature detection and orientation tuning in the Drosophila central complex.}, journal = {Nature}, volume = {503}, year = {2013}, month = {2013 Oct 9}, pages = {262-66}, abstract = {

Many animals, including insects, are known to use visual landmarks to orient in their environment. In Drosophila melanogaster, behavioural genetics studies have identified a higher brain structure called the central complex as being required for the fly{\textquoteright}s innate responses to vertical visual features and its short- and long-term memory for visual patterns. But whether and how neurons of the fly central complex represent visual features are unknown. Here we use two-photon calcium imaging in head-fixed walking and flying flies to probe visuomotor responses of ring neurons{\textemdash}a class of central complex neurons that have been implicated in landmark-driven spatial memory in walking flies and memory for visual patterns in tethered flying flies. We show that dendrites of ring neurons are visually responsive and arranged retinotopically. Ring neuron receptive fields comprise both excitatory and inhibitory subfields, resembling those of simple cells in the mammalian primary visual cortex. Ring neurons show strong and, in some cases, direction-selective orientation tuning, with a notable preference for vertically oriented features similar to those that evoke innate responses in flies. Visual responses were diminished during flight, but, in contrast with the hypothesized role of the central complex in the control of locomotion, not modulated during walking. Taken together, these results indicate that ring neurons represent behaviourally relevant visual features in the fly{\textquoteright}s environment, enabling downstream central complex circuits to produce appropriate motor commands. More broadly, this study opens the door to mechanistic investigations of circuit computations underlying visually guided action selection in the Drosophila central complex.

}, issn = {1476-4687}, doi = {10.1038/nature12601}, author = {Seelig, Johannes D and Jayaraman, Vivek} } @article {5305, title = {Studying sensorimotor processing with physiology in behaving Drosophila.}, journal = {International Review of Neurobiology}, volume = {99}, year = {2011}, month = {2011}, pages = {169-89}, abstract = {

The neural underpinnings of sensorimotor integration are best studied in the context of well-characterized behavior. A rich trove of Drosophila behavioral genetics research offers a variety of well-studied behaviors and candidate brain regions that can form the bases of such studies. The development of tools to perform in vivo physiology from the Drosophila brain has made it possible to monitor activity in defined neurons in response to sensory stimuli. More recently still, it has become possible to perform recordings from identified neurons in the brain of head-fixed flies during walking or flight behaviors. In this chapter, we discuss how experiments that simultaneously monitor behavior and physiology in Drosophila can be combined with other techniques to produce testable models of sensorimotor circuit function.

}, keywords = {Animal, Animals, Behavior, Brain, Drosophila, Electrophysiology, Motivation, Neurons, Psychomotor Performance}, issn = {0074-7742}, doi = {10.1016/B978-0-12-387003-2.00007-0}, author = {Seelig, Johannes D and Jayaraman, Vivek} } @article {1645, title = {Two-photon calcium imaging from head-fixed Drosophila during optomotor walking behavior.}, journal = {Nature Methods}, volume = {7}, year = {2010}, month = {2010 Jul}, pages = {535-40}, abstract = {

Drosophila melanogaster is a model organism rich in genetic tools to manipulate and identify neural circuits involved in specific behaviors. Here we present a technique for two-photon calcium imaging in the central brain of head-fixed Drosophila walking on an air-supported ball. The ball{\textquoteright}s motion is tracked at high resolution and can be treated as a proxy for the fly{\textquoteright}s own movements. We used the genetically encoded calcium sensor, GCaMP3.0, to record from important elements of the motion-processing pathway, the horizontal-system lobula plate tangential cells (LPTCs) in the fly optic lobe. We presented motion stimuli to the tethered fly and found that calcium transients in horizontal-system neurons correlated with robust optomotor behavior during walking. Our technique allows both behavior and physiology in identified neurons to be monitored in a genetic model organism with an extensive repertoire of walking behaviors.

}, keywords = {Animals, Brain, Calcium, Computer-Assisted, Drosophila melanogaster, Fluorescence, Green Fluorescent Proteins, Image Processing, Motion, Motor Activity, Neurons, Signal Transduction, Walking}, issn = {1548-7105}, doi = {10.1038/nmeth.1468}, author = {Seelig, Johannes D and Chiappe, M Eugenia and Lott, Gus K and Dutta, Anirban and Osborne, Jason E and Reiser, Michael B and Jayaraman, Vivek} } @article {3759, title = {Walking modulates speed sensitivity in Drosophila motion vision.}, journal = {Current Biology}, volume = {20}, year = {2010}, month = {2010 Aug 24}, pages = {1470-5}, abstract = {

Changes in behavioral state modify neural activity in many systems. In some vertebrates such modulation has been observed and interpreted in the context of attention and sensorimotor coordinate transformations. Here we report state-dependent activity modulations during walking in a visual-motor pathway of Drosophila. We used two-photon imaging to monitor intracellular calcium activity in motion-sensitive lobula plate tangential cells (LPTCs) in head-fixed Drosophila walking on an air-supported ball. Cells of the horizontal system (HS){\textendash}a subgroup of LPTCs{\textendash}showed stronger calcium transients in response to visual motion when flies were walking rather than resting. The amplified responses were also correlated with walking speed. Moreover, HS neurons showed a relatively higher gain in response strength at higher temporal frequencies, and their optimum temporal frequency was shifted toward higher motion speeds. Walking-dependent modulation of HS neurons in the Drosophila visual system may constitute a mechanism to facilitate processing of higher image speeds in behavioral contexts where these speeds of visual motion are relevant for course stabilization.

}, keywords = {Animals, Calcium, Calcium Signaling, Drosophila, Motion Perception, Photic Stimulation, Walking}, issn = {1879-0445}, doi = {10.1016/j.cub.2010.06.072}, author = {Chiappe, M Eugenia and Seelig, Johannes D and Reiser, Michael B and Jayaraman, Vivek} }