NEUROSCIENCE THROUGH THE LENS OF BEHAVIOR (2010-2016)
[N15] The velocity-curvature power law in Drosophila larval locomotion
Myrka Zago, Francesco Lacquaniti, Alex Gomez-Marin
bioRxiv eprint — under review (2016)
[N14] Hierarchical compression of C. elegans locomotion reveals phenotypic differences in the organization of behaviour
Alex Gomez-Marin, Greg J. Stephens, André E.X. Brown (2016)
J. R. Soc. Interface 13: 20160466
Regularities in animal behaviour offer insight into the underlying organizational and functional principles of nervous systems and automated tracking provides the opportunity to extract features of behaviour directly from large-scale video data. Yet how to effectively analyse such behavioural data remains an open question. Here we explore whether a minimum description length principle can be exploited to identify meaningful behaviours and phenotypes. We apply a dictionary compression algorithm to behavioural sequences from the nematode worm Caenorhabditis elegans freely crawling on an agar plate both with and without food and during chemotaxis. We find that the motifs identified by the compression algorithm are rare but relevant for comparisons between worms in different environments, suggesting that hierarchical compression can be a useful step in behaviour analysis. We also use compressibility as a new quantitative phenotype and find that the behaviour of wild-isolated strains of C. elegans is more compressible than that of the laboratory strain N2 as well as the majority of mutant strains examined. Importantly, in distinction to more conventional phenotypes such as overall motor activity or aggregation behaviour, the increased compressibility of wild isolates is not explained by the loss of function of the gene npr-1, which suggests that erratic locomotion is a laboratory-derived trait with a novel genetic basis. Because hierarchical compression can be applied to any sequence, we anticipate that compressibility can offer insight into the organization of behaviour in other animals including humans.
[N13] Generative rules of Drosophila locomotor behavior as a candidate homology across phyla
[link][pdf][preprint] Extra: [movie warmup] [movie shutdown] [animation warmup] [animation shutdown]
Alex Gomez-Marin*, Efrat Oron, Anna Gakamsky, Dan Valente, Yoav Benjamini, Ilan Golani* (2016)
Sci. Rep. 6, 27555
The discovery of shared behavioral processes across phyla is a significant step in the establishment of a comparative study of behavior. We use immobility as an origin and reference for the measurement of fly locomotor behavior; speed, walking direction and trunk orientation as the degrees of freedom shaping this behavior; and cocaine as the parameter inducing progressive transitions in and out of immobility. We characterize and quantify the generative rules that shape Drosophila locomotor behavior, bringing about a gradual buildup of kinematic degrees of freedom during the transition from immobility to normal behavior, and the opposite narrowing down into immobility. Transitions into immobility unfold via sequential enhancement and then elimination of translation, curvature and finally rotation. Transitions out of immobility unfold by progressive addition of these degrees of freedom in the opposite order. The same generative rules have been found in vertebrate locomotor behavior in several contexts (pharmacological manipulations, ontogeny, social interactions) involving transitions in-and-out of immobility. Recent claims for deep homology between arthropod central complex and vertebrate basal ganglia provide an opportunity to examine whether the rules we report also share common descent. Our approach prompts the discovery of behavioral homologies, contributing to the elusive problem of behavioral evolution.
[N12] Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes
Aris Polyzos, Amy Holt, Christopher Brown, Celica Cosme, Peter Wipf, Alex Gomez-Marin, María del R. Castro, Sylvette Ayala-Peña, and Cynthia T. McMurray (2016)
Human Molecular Genetics, 1-11
Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington’s disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a graying phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.
[N11] Expanding perspectives on cognition in humans, animals, and machines
Alex Gomez-Marin*, Zachary F Mainen* (2016)
Current Opinion in Neurobiology 37:85–91
Over the past decade neuroscience has been attacking the problem of cognition with increasing vigor. Yet, what exactly is cognition, beyond a general signifier of anything seemingly complex the brain does? Here, we briefly review attempts to define, describe, explain, build, enhance and experience cognition. We highlight perspectives including psychology, molecular biology, computation, dynamical systems, machine learning, behavior and phenomenology. This survey of the landscape reveals not a clear target for explanation but a pluralistic and evolving scene with diverse opportunities for grounding future research. We argue that rather than getting to the bottom of it, over the next century, by deconstructing and redefining cognition, neuroscience will and should expand rather than merely reduce our concept of the mind.
[N10] Dynamical feature extraction at the sensory periphery guides chemotaxis
[link] [pdf] Extra: [eLIFE insight] [news El Pais] [news La Vanguardia]
Aljoscha Schulze*, Alex Gomez-Marin*, Vani G Rajendran, Gus Lott, Marco Musy, Parvez Ahammad, Ajinkya Deogade, James Sharpe, Julia Riedl, David Jarriault, Eric T Trautman, Christopher Werner, Madhusudhan Venkadesan, Shaul Druckmann, Vivek Jayaraman, Matthieu Louis (2015)
Behavioral strategies employed for chemotaxis have been described across phyla, but the sensorimotor basis of this phenomenon has seldom been studied in naturalistic contexts. Here, we examine how signals experienced during free olfactory behaviors are processed by first-order olfactory sensory neurons (OSNs) of the Drosophila larva. We find that OSNs can act as differentiators that transiently normalize stimulus intensity—a property potentially derived from a combination of integral feedback and feed-forward regulation of olfactory transduction. In olfactory virtual reality experiments, we report that high activity levels of the OSN suppress turning, whereas low activity levels facilitate turning. Using a generalized linear model, we explain how peripheral encoding of olfactory stimuli modulates the probability of switching from a run to a turn. Our work clarifies the link between computations carried out at the sensory periphery and action selection underlying navigation in odor gradients.
[N9] Role of the Subesophageal Zone in Sensorimotor Control of Orientation in Drosophila Larva
Ibrahim Tastekin*, Julia Riedl*, Verena Schilling-Kurz, Alex Gomez-Marin, James W. Truman, Matthieu Louis (2015)
Current Biology 25: 11 p.1448–1460
Chemotaxis is a powerful paradigm to investigate how nervous systems represent and integrate changes in sensory signals to direct navigational de- cisions. In the Drosophila melanogaster larva, chemotaxis mainly consists of an alternation of distinct behavioral modes: runs and directed turns. During locomotion, turns are triggered by the integra- tion of temporal changes in the intensity of the stim- ulus. Upon completion of a turning maneuver, the direction of motion is typically realigned toward the odor gradient. While the anatomy of the peripheral ol- factory circuits and the locomotor system of the larva are reasonably well documented, the neural circuits connecting the sensory neurons to the motor neurons remain unknown. We combined a loss-of-function behavioral screen with optogenetics-based clonal gain-of-function manipulations to identify neurons that are necessary and sufficient for the initiation of reorientation maneuvers in odor gradients. Our re- sults indicate that a small subset of neurons residing in the subesophageal zone controls the rate of transi- tion from runs to turns—a premotor function compat- ible with previous observations made in other inverte- brates. After having shown that this function pertains to the processing of inputs from different sensory modalities (olfaction, vision, thermosensation), we conclude that the subesophageal zone operates as a general premotor center that regulates the selection of different behavioral programs based on the inte- gration of sensory stimuli. The present analysis paves the way for a systematic investigation of the neural computations underlying action selection in a minia- ture brain amenable to genetic manipulations.
[N8] Big Behavioral Data: Psychology, Ethology and the Foundations of Neuroscience
[link] [pdf] Extra: [editorial]
Alex Gomez-Marin, Joseph J Paton, Adam R Kampff, Rui M Costa, Zachary M Mainen (2014)
Nature Neuroscience 17, 1455–1462
Behavior is a unifying organismal process where genes, neural function, anatomy and environment converge and interrelate. Here we review the current state and discuss the future impact of accelerating advances in technology for behavioral studies, focusing on rodents as an exemplar. We frame our perspective in three dimensions: degree of experimental constraint, dimensionality of data, and level of description. We argue that “big behavioral data” presents challenges proportionate to its promise and describe how these challenges might be met through opportunities afforded by the two rival conceptual legacies of 20th century behavioral science, ethology and psychology. We conclude that although “more is not necessarily better”, copious, quantitative and open behavioral data has the potential to transform and unify these two disciplines and to solidify the foundations of others, including neuroscience, but only if the development of novel theoretical frameworks and improved experimental designs matches the technological progress.
[N7] Multilevel control of run orientation in Drosophila larval chemotaxis
Alex Gomez-Marin*, Matthieu Louis* (2014)
Frontiers in Behavioral Neuroscience 8:38
Chemotaxis is a powerful paradigm to study how orientation behavior is driven by sensory stimulation. Drosophila larvae navigate odor gradients by controlling the duration of their runs and the direction of their turns. Straight runs and wide-amplitude turns represent two extremes of a behavioral continuum. Here we establish that, on average, runs curl toward the direction of higher odor concentrations. We find that the orientation and strength of the local odor gradient perpendicular to the direction of motion modulates the orientation of individual runs in a gradual manner. We discuss how this error-correction mechanism, called weathervaning, contributes to larval chemotaxis. We use larvae with a genetically modified olfactory system to demonstrate that unilateral function restricted to a single olfactory sensory neuron (OSN) is sufficient to direct weathervaning. Our finding that bilateral sensing is not necessary to control weathervaning highlights the role of temporal sampling. A correlational analysis between sensory inputs and behavioral outputs suggests that weathervaning results from low-amplitude head casts implemented without interruption of the run. In addition, we report the involvement of a sensorimotor memory arising from previous reorientation events. Together, our results indicate that larval chemotaxis combines concurrent orientation strategies that involve complex computations on different timescales.
[N6] Tools, flies and what to do next
Alex Gomez-Marin (2013)
American Institute of Physics Conf. Proc. 1510, 120
In these brief notes addressed to students and researchers, recent advances of modern neurobiology are discussed in the light of some of its challenges. I use fly larval chemotaxis as a platform to debate about how much we are able to do with the available tools as opposed to how little we actually understand what it means to decide.
[N5] A simple method to study Drosophila leg movements during free climbing
[link] Extra: [movie]
Alex Gomez-Marin*, B. Iyengar* (2012)
Exquisite new automated methods are now available to track the leg movements of Drosophila during walking and grooming behaviors. The tethered approach is most suitable for parallel functional-imaging of the brain . Simpler, but yet effective automated protocols for analyzing walking kinematics of any insect, crustacean or arachnid at the level of leg swing and stance states will be very useful not only for data-mining towards bio-robotics applications but also for high throughput screening for neurological effects. With regard to Drosophila walking behaviour, accurate automated measurements of gait parameters will facilitate a better characterization of the genetic basis of nervous system disorders. Here, we attempted to utilize the leg-shape-feature along the body contour to automatically track the identity and movement of each leg during a free-climbing episode inside a transparent curved glass tube.
[N4] Automated tracking of animal posture and movement during exploration and sensory orientation behaviors
[link] [pdf] Extra: [movie] [code] [news Science Daily] [news Europa Press]
Alex Gomez-Marin*, N. Partoune, G.J. Stephens, M. Louis* (2012)
PLoS ONE 7 (8): e41642
We present Sensory Orientation Software (SOS) to measure behavior and infer sensory experience correlates. SOS is a simple and versatile system to track body posture and motion of single animals in two-dimensional environments. In the presence of a sensory landscape, tracking the trajectory of the animal’s sensors and its postural evolution provides a quantitative framework to study sensorimotor integration. To illustrate the utility of SOS, we examine the orientation behavior of fruit fly larvae in response to odor, temperature and light gradients. We show that SOS is suitable to carry out high-resolution behavioral tracking for a wide range of organisms including flatworms, fishes and mice. Our work contributes to the growing repertoire of behavioral analysis tools for collecting rich and fine-grained data to draw and test hypothesis about the functioning of the nervous system. By providing open-access to our code and documenting the software design, we aim to encourage the adaptation of SOS by a wide community of non-specialists to their particular model organism and questions of interest.
[N3] Active sensation during orientation behavior in the Drosophila larva: more sense than luck
Alex Gomez-Marin, M. Louis (2012)
Current Opinion in Neurobiology 22:1-8
The fruit fly Drosophila larva demonstrates a sophisticated repertoire of behavior under the control of a numerically simple neural system. Historically, the stereotyped responses of larvae to light and odors captivated the attention of biologists. More recently, the sensory receptors responsible for chemosensation, thermosensation, and vision have been identified. While our understanding of the molecular logic of perception has clearly progressed, little is known about the neural and computational mechanisms guiding movement in sensory gradients. Here we review evidence that larvae orient based on active sensation — a feature distinct from the strategies used by simpler model organisms. Reorientation maneuvers are controlled by the spatiotemporal integration of changes in stimulus intensity detected during runs and lateral head movements.
[N2] Active sampling and decision making in Drosophila chemotaxis
[link] [pdf] Extra: [news Lukor] [news Ecoticias]
Alex Gomez-Marin, G.J. Stephens, M. Louis (2011)
Nature Communications 2:441
The ability to respond to chemical stimuli is fundamental to the survival of motile organisms, but the strategies underlying odour tracking remain poorly understood. Here we show that chemotaxis inDrosophila melanogaster larvae is an active sampling process analogous to sniffing in vertebrates. Combining computer-vision algorithms with reconstructed olfactory environments, we establish that larvae orient in odour gradients through a sequential organization of stereotypical behaviours, including runs, stops, lateral head casts and directed turns. Negative gradients, integrated during runs, control the timing of turns. Positive gradients detected through high-amplitude head casts determine the direction of individual turns. By genetically manipulating the peripheral olfactory circuit, we examine how orientation adapts to losses and gains of function in olfactory input. Our findings suggest that larval chemotaxis represents an intermediate navigation strategy between the biased random walks of Escherichia Coli and the stereo-olfaction observed in rats and humans.
[N1] Mechanisms of odor-tracking: multiple sensors for enhanced perception and behavior
Alex Gomez-Marin*, B.J. Duistermars*, M.A. Frye, M. Louis (2010)
Frontiers in Cellular Neuroscience 4:6
Early in evolution, the ability to sense and respond to changing environments must have provided a critical survival advantage to living organisms. From bacteria and worms to flies and vertebrates, sophisticated mechanisms have evolved to enhance odor detection and localization. Here, we review several modes of chemotaxis. We further consider the relevance of a striking and recurrent motif in the organization of invertebrate and vertebrate sensory systems, namely the existence of two symmetrical olfactory sensors. By combining our current knowledge about the olfactory circuits of larval and adult Drosophila, we examine the molecular and neural mechanisms underlying robust olfactory perception and extend these analyses to recent behavioral studies addressing the relevance and function of bilateral olfactory input for gradient detection. Finally, using a comparative theoretical approach based on Braitenberg’s vehicles, we speculate about the relationships between anatomy, circuit architecture and stereotypical orientation behaviors.