INAUGURAL ARTICLE by a Recently Elected Academy Member:A circuit for navigation in Caenorhabditis elegans

As an animal travels through its environment, its nervous system detects sensory cues, evaluates them based on context and the experience of the animal, and converts this information into adaptive movement. For simple behaviors, sensory neurons sometimes communicate directly with motor neurons, but, in more complex behavioral circuits, several layers of interneurons integrate sensory information and relay it to motor neurons. The path from sensory input to motor output has been defined in only a few cases, including circuits for crustacean feeding (1) and circuits for rapid escape in fish, flies, and nematodes (2–4). In the nematode Caenorhabditis elegans, the escape circuit was defined by using a complete synaptic wiring diagram of the 302 neurons in its nervous system (4, 5). Six mechanosensory neurons that detect noxious stimuli synapse onto four pairs of interneurons called forward and backward command neurons. The command neurons synapse in turn onto motor neurons responsible for forward and backward locomotion, leading to rapid withdrawal from the stimulus. The definition of the escape circuit has enabled analysis of its development, regulation, and modification by experience (6–11). The C. elegans wiring diagram provides an opportunity to define many complete neuronal paths from sensory stimulus to behavior. In contrast with the escape circuit, the neuronal control of locomotion during exploratory behavior is poorly characterized. C. elegans navigates to favorable conditions by chemotaxis, thermotaxis, and aerotaxis. In these sensory behaviors and in exploratory behaviors in the absence of informative sensory cues, the animal moves forward and occasionally changes its direction of movement either by a transient reversal or by turning its head during forward movement. The largest change in direction is generated in a sharp omega turn during which the animal's body shape resembles the Greek letter Ω (12, 13) (Fig. 1A). Sinusoidal movement itself can also change during navigation, switching between shallow and deep bends. The neuronal pathways that convert sensory information into specific turning behaviors are incompletely defined. The command neurons are not required for the generation of sinusoidal forward movement (4, 11); the neurons that modulate forward movement to cause curving and omega turns are unknown. Fig. 1. Regulation of reversals and omega turns during feeding, local search, and dispersal. (A) Four different examples of reversals of different lengths and degrees of reorientation. Tracks are visible as indentations in the agar. r1, reversal with a single . In C. elegans, taxis behaviors have features of a biased random walk (14–16) (J.M.G. and C.I.B., unpublished data), a strategy first described in bacterial chemotaxis (17). During a biased random walk, periods of relatively straight movement (“runs”) are occasionally interrupted by periods of rapid direction change (“tumbles” in bacteria and “pirouettes” in C. elegans). A pirouette is a period marked by reversals or sharp turns (14). In a biased random walk, individual trajectories are not predictable. However, when the environment is improving (e.g., when concentrations of attractant increase), pirouettes become less frequent. When the environment is declining, pirouettes become more frequent. This strategy biases the direction of travel toward favorable conditions. We sought to understand the mechanisms by which sensory neurons modulate the frequency of reversals and turns in C. elegans and the downstream neuronal circuits that generate specific features of these behaviors. The presence of food affects many aspects of C. elegans locomotion (18–21). Here we use a systematic analysis of C. elegans neuroanatomy to dissect a circuit that uses sensory cues to modulate turning rates in two kinds of exploratory behavior: local search after animals are removed from food and long-range dispersal after prolonged food deprivation. These exploratory behaviors in the absence of directional cues share many features with a biased random walk. Our results delineate a behavioral circuit for navigation in C. elegans from sensory input to motor output.