A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans

Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms

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

An Image-Free Opto-Mechanical System for Creating Virtual Environments and Imaging Neuronal Activity in Freely Moving Caenorhabditis elegans

Non-invasive recording in untethered animals is arguably the ultimate step in the analysis of neuronal function, but such recordings remain elusive. To address this problem, we devised a system that tracks neuron-sized fluorescent targets in real time. The system can be used to create virtual environments by optogenetic activation of sensory neurons, or to image activity in identified neurons at high magnification. By recording activity in neurons of freely moving C. elegans, we tested the long-standing hypothesis that forward and reverse locomotion are generated by distinct neuronal circuits. Surprisingly, we found motor neurons that are active during both types of locomotion, suggesting a new model of locomotion control in C. elegans. These results emphasize the importance of recording neuronal activity in freely moving animals and significantly expand the potential of imaging techniques by providing a mean to stabilize fluorescent targets

Step Response Analysis of Thermotaxis in Caenorhabditis

Introduction Caenorhabditis elegans orients to both chemical (chemotaxis) and thermal (thermotaxis) gradients (Ward, 1973; Hedgecock and Russell, 1975), making it a promising experimental system for investigating the neuronal basis of spatial orientation. Previous studies have established a plausible behavioral mechanism for chemotaxis in C. elegans (Dusenbery, 1980; Pierce-Shimomura et al., 1999). Locomotion consists of periods of relatively straightforward movement punctuated approximately twice per minute by bouts of turning (Rutherford and Croll, 1979). Two main kinds of turns are recognized in C. elegans: "reversals," in which the animal moves backward for several seconds and then goes forward again in a new direction, and "omega turns," in which the animal's head bends around to touch the tail during forward locomotion, momentarily forming a shape like the Greek letter (Croll, 1975b). Statistical analysis reveals that reversals and omega turns occur in bursts that have been ter

Lateralized Gustatory Behavior of C. elegans Is Controlled by Specific Receptor-Type Guanylyl Cyclases

SummaryBackgroundEven though functional lateralization is a common feature of many nervous systems, it is poorly understood how lateralized neural function is linked to lateralized gene activity. A bilaterally symmetric pair of C. elegans gustatory neurons, ASEL and ASER, senses a number of chemicals in a left/right asymmetric manner and therefore serves as a model to study the genetic basis of functional lateralization. The extent of functional lateralization of the ASE neurons and genes responsible for the left/right asymmetric activity of ASEL and ASER is unknown.ResultsWe show here that a substantial number of salt ions are sensed in a left/right asymmetric manner and that lateralized salt responses allow the worm to discriminate between distinct salt cues. To identify molecules that may be involved in sensing salt ions and/or transmitting such sensory information, we examined the chemotaxis behavior of animals harboring mutations in eight different receptor-type, transmembrane guanylyl cyclases (encoded by gcy genes), which are expressed in either ASEL (gcy-6, gcy-7, gcy-14), ASER (gcy-1, gcy-4, gcy-5, gcy-22), or ASEL and ASER (gcy-19). Disruption of a particular ASER-expressed gcy gene, gcy-22, results in a broad chemotaxis defect to nearly all salts sensed by ASER, as well as to a left/right asymmetrically sensed amino acid. In contrast, disruption of other gcy genes resulted in highly salt ion-specific chemosensory defects.ConclusionsOur findings broaden our understanding of lateralities in neural function, provide insights into how this laterality is molecularly encoded, and reveal an unusual multitude of molecules involved in gustatory signal transduction