Shared Strategies for Behavioral Switching: Understanding How Locomotor Patterns are Turned on and Off

Animals frequently switch from one behavior to another, often to meet the demands of their changing environment or internal state. What factors control these behavioral switches and the selection of what to do or what not to do? To address these issues, we will focus on the locomotor behaviors of two distantly related “worms,” the medicinal leech Hirudo verbana (clade Lophotrochozoa) and the nematode Caenorhabditis elegans (clade Ecdysozoa). Although the neural architecture and body morphology of these organisms are quite distinct, they appear to switch between different forms of locomotion by using similar strategies of decision-making. For example, information that distinguishes between liquid and more solid environments dictates whether an animal swims or crawls. In the leech, dopamine biases locomotor neural networks so that crawling is turned on and swimming is turned off. In C. elegans, dopamine may also promote crawling, a form of locomotion that has gained new attention

Long-tail Behavior in Locomotion of Caenorhabditis elegans

The locomotion of Caenorhabditis elegans exhibits complex patterns. In particular, the worm combines mildly curved runs and sharp turns to steer its course. Both runs and sharp turns of various types are important components of taxis behavior. The statistics of sharp turns have been intensively studied. However, there have been few studies on runs, except for those on klinotaxis (also called weathervane mechanism), in which the worm gradually curves toward the direction with a high concentration of chemicals; this phenomenon was discovered recently. We analyzed the data of runs by excluding sharp turns. We show that the curving rate obeys long-tail distributions, which implies that large curving rates are relatively frequent. This result holds true for locomotion in environments both with and without a gradient of NaCl concentration; it is independent of klinotaxis. We propose a phenomenological computational model on the basis of a random walk with multiplicative noise. The assumption of multiplicative noise posits that the fluctuation of the force is proportional to the force exerted. The model reproduces the long-tail property present in the experimental data.Comment: 30 pages, 11 figures, some errors were correcte

Manipulation of Behavioral Decline in Caenorhabditis elegans with the Rag GTPase raga-1

Normal aging leads to an inexorable decline in motor performance, contributing to medical morbidity and decreased quality of life. While much has been discovered about genetic determinants of lifespan, less is known about modifiers of age-related behavioral decline and whether new gene targets may be found which extend vigorous activity, with or without extending lifespan. Using Caenorhabditis elegans, we have developed a model of declining neuromuscular function and conducted a screen for increased behavioral activity in aged animals. In this model, behavioral function suffers from profound reductions in locomotory frequency, but coordination is strikingly preserved until very old age. By screening for enhancers of locomotion at advanced ages we identified the ras-related Rag GTPase raga-1 as a novel modifier of behavioral aging. raga-1 loss of function mutants showed vigorous swimming late in life. Genetic manipulations revealed that a gain of function raga-1 curtailed behavioral vitality and shortened lifespan, while a dominant negative raga-1 lengthened lifespan. Dietary restriction results indicated that a raga-1 mutant is relatively protected from the life-shortening effects of highly concentrated food, while RNAi experiments suggested that raga-1 acts in the highly conserved target of rapamycin (TOR) pathway in C. elegans. Rag GTPases were recently shown to mediate nutrient-dependent activation of TOR. This is the first demonstration of their dramatic effects on behavior and aging. This work indicates that novel modulators of behavioral function can be identified in screens, with implications for future study of the clinical amelioration of age-related decline

The Dystrophin Complex Controls BK Channel Localization and Muscle Activity in Caenorhabditis elegans

Genetic defects in the dystrophin-associated protein complex (DAPC) are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC components from humans to Caenorhabditis elegans suggest a similar molecular function. C. elegans DAPC mutants exhibit a unique locomotory deficit resulting from prolonged muscle excitation and contraction. Here we show that the C. elegans DAPC is essential for proper localization of SLO-1, the large conductance, voltage-, and calcium-dependent potassium (BK) channel, which conducts a major outward rectifying current in muscle under the normal physiological condition. Through analysis of mutants with the same phenotype as the DAPC mutants, we identified the novel islo-1 gene that encodes a protein with two predicted transmembrane domains. We demonstrate that ISLO-1 acts as a novel adapter molecule that links the DAPC to SLO-1 in muscle. We show that a defect in either the DAPC or ISLO-1 disrupts normal SLO-1 localization in muscle. Consistent with observations that SLO-1 requires a high calcium concentration for full activation, we find that SLO-1 is localized near L-type calcium channels in muscle, thereby providing a mechanism coupling calcium influx with the outward rectifying current. Our results indicate that the DAPC modulates muscle excitability by localizing the SLO-1 channel to calcium-rich regions of C. elegans muscle

An imaging system for standardized quantitative analysis of C. elegans behavior

BACKGROUND: The nematode Caenorhabditis elegans is widely used for the genetic analysis of neuronal cell biology, development, and behavior. Because traditional methods for evaluating behavioral phenotypes are qualitative and imprecise, there is a need for tools that allow quantitation and standardization of C. elegans behavioral assays. RESULTS: Here we describe a tracking and imaging system for the automated analysis of C. elegans morphology and behavior. Using this system, it is possible to record the behavior of individual nematodes over long time periods and quantify 144 specific phenotypic parameters. CONCLUSIONS: These tools for phenotypic analysis will provide reliable, comprehensive scoring of a wide range of behavioral abnormalities, and will make it possible to standardize assays such that behavioral data from different labs can readily be compared. In addition, this system will facilitate high-throughput collection of phenotypic data that can ultimately be used to generate a comprehensive database of C. elegans phenotypic information. AVAILABILITY: The hardware configuration and software for the system are available from [email protected]

Intermittent search strategies

This review examines intermittent target search strategies, which combine phases of slow motion, allowing the searcher to detect the target, and phases of fast motion during which targets cannot be detected. We first show that intermittent search strategies are actually widely observed at various scales. At the macroscopic scale, this is for example the case of animals looking for food ; at the microscopic scale, intermittent transport patterns are involved in reaction pathway of DNA binding proteins as well as in intracellular transport. Second, we introduce generic stochastic models, which show that intermittent strategies are efficient strategies, which enable to minimize the search time. This suggests that the intrinsic efficiency of intermittent search strategies could justify their frequent observation in nature. Last, beyond these modeling aspects, we propose that intermittent strategies could be used also in a broader context to design and accelerate search processes.Comment: 72 pages, review articl

Single-cell transcriptional analysis of taste sensory neuron pair in Caenorhabditis elegans

The nervous system is composed of a wide variety of neurons. A description of the transcriptional profiles of each neuron would yield enormous information about the molecular mechanisms that define morphological or functional characteristics. Here we show that RNA isolation from single neurons is feasible by using an optimized mRNA tagging method. This method extracts transcripts in the target cells by co-immunoprecipitation of the complexes of RNA and epitope-tagged poly(A) binding protein expressed specifically in the cells. With this method and genome-wide microarray, we compared the transcriptional profiles of two functionally different neurons in the main C. elegans gustatory neuron class ASE. Eight of the 13 known subtype-specific genes were successfully detected. Additionally, we identified nine novel genes including a receptor guanylyl cyclase, secreted proteins, a TRPC channel and uncharacterized genes conserved among nematodes, suggesting the two neurons are substantially different than previously thought. The expression of these novel genes was controlled by the previously known regulatory network for subtype differentiation. We also describe unique motif organization within individual gene groups classified by the expression patterns in ASE. Our study paves the way to the complete catalog of the expression profiles of individual C. elegans neurons

Searching for simplicity: Approaches to the analysis of neurons and behavior

What fascinates us about animal behavior is its richness and complexity, but understanding behavior and its neural basis requires a simpler description. Traditionally, simplification has been imposed by training animals to engage in a limited set of behaviors, by hand scoring behaviors into discrete classes, or by limiting the sensory experience of the organism. An alternative is to ask whether we can search through the dynamics of natural behaviors to find explicit evidence that these behaviors are simpler than they might have been. We review two mathematical approaches to simplification, dimensionality reduction and the maximum entropy method, and we draw on examples from different levels of biological organization, from the crawling behavior of C. elegans to the control of smooth pursuit eye movements in primates, and from the coding of natural scenes by networks of neurons in the retina to the rules of English spelling. In each case, we argue that the explicit search for simplicity uncovers new and unexpected features of the biological system, and that the evidence for simplification gives us a language with which to phrase new questions for the next generation of experiments. The fact that similar mathematical structures succeed in taming the complexity of very different biological systems hints that there is something more general to be discovered

Ammonium-Acetate Is Sensed by Gustatory and Olfactory Neurons in Caenorhabditis elegans

Background: Caenorhabditis elegans chemosensation has been successfully studied using behavioral assays that treat detection of volatile and water soluble chemicals as separate senses, analogous to smell and taste. However, considerable ambiguity has been associated with the attractive properties of the compound ammonium-acetate (NH 4Ac). NH 4Ac has been used in behavioral assays both as a chemosensory neutral compound and as an attractant. Methodology/Main Findings: Here we show that over a range of concentrations NH4Ac can be detected both as a water soluble attractant and as an odorant, and that ammonia and acetic acid individually act as olfactory attractants. We use genetic analysis to show that NaCl and NH4Ac sensation are mediated by separate pathways and that ammonium sensation depends on the cyclic nucleotide gated ion channel TAX-2/TAX-4, but acetate sensation does not. Furthermore we show that sodium-acetate (NaAc) and ammonium-chloride (NH4Cl) are not detected as Na + and Cl 2 specific stimuli, respectively. Conclusions/Significance: These findings clarify the behavioral response of C. elegans to NH4Ac. The results should have an impact on the design and interpretation of chemosensory experiments studying detection and adaptation to soluble compounds in the nematode Caenorhabditis elegans