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The Circuit for Chemotaxis and Exploratory Behavior in C. elegans 

The Circuit for Chemotaxis and Exploratory Behavior in C. elegans
Chapter:
The Circuit for Chemotaxis and Exploratory Behavior in C. elegans
Author(s):

Cornelia I. Bargmann

DOI:
10.1093/med/9780195389883.003.0051
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Over 20 years ago, a wiring diagram of the C. elegans nervous system was constructed from serial-section electron micrographs (White et al., 1986). The 302 neurons in the nervous system of the adult hermaphrodite consist of three overall classes: sensory neurons with specialized cilia or dendrites, motor neurons that form neuromuscular junctions, and interneurons that connect sensory neurons with motor neurons. Most sensory neurons and interneurons belong to bilaterally symmetric pairs with similar connections and morphologies, while many motor neurons belong to larger classes. The C. elegans nervous system presents an unusual situation in which neuroanatomical connections are extremely well defined, but the understanding of neuronal activity is fragmentary.

One C. elegans circuit that is relatively well characterized generates undirected search when animals are removed from food, and directed chemotaxis in odor gradients. Both of these behaviors are based upon temporally regulated turning behavior (Pierce-Shimomura et al., 1999; Hills et al., 2004; Wakabayashi et al., 2004; Gray et al., 2005). When animals are removed from food, a transient turning bout produces undirected local search (Tsalik and Hobert, 2003; Zhao et al., 2003; Hills et al., 2004; Wakabayashi et al., 2004; Gray et al., 2005). The turning bout lasts about 15 minutes and keeps animals in a restricted area; thereafter, suppression of turning results in dispersal. In the presence of an odor gradient, fine-grained temporally regulated turns produce a biased random walk for gradient climbing (Pierce-Shimomura et al., 1999). During chemotaxis, increases in odor levels transiently suppress turning, and decreases in odor levels increase turning.

The wiring diagram and quantitative behavioral analysis have been used to trace the circuit for local search behavior from sensory input to motor output (Gray et al., 2005) (Fig. 51.1). Based on cell ablations, some neuronsstimulate turning—killing them leads to reduced turning during local search. The most important of these are AWC sensory neurons and AIB interneurons. Other neurons inhibit turning—killing them leads to increased turning during local search and/or dispersal. The most important of these are AIA and AIY interneurons. Several neurons such as RIM have mixed properties, stimulating some classes of turns while inhibiting others. AWC sensory neurons trigger both exploratory behavior and chemotaxis; the downstream interneurons have overlapping, but not identical roles in the two behaviors.

Figure 51–1. Turning circuit for chemotaxis and exploratory behavior. Sensory neurons are denoted as triangles, interneurons as hexagons, and motor neurons as circles. Blue neurons stimulate turning; red neurons inhibit turning; black neurons have mixed activity; gray neurons are untested (Gray et al., 2005). Black lines indicate excitatory (arrow) and inhibitory (stopped) synapses or synaptic inputs established by calcium imaging (Chalasani et al., 2007; Macosko et al., 2009). Dashed lines indicate sites of neuromodulation (Zhang et al., 2005; Tsunozaki et al., 2008). Gray arrows indicate anatomically predicted, but functionally unconfirmed connections from the wiring diagram (White et al., 1986).

Figure 51–1.
Turning circuit for chemotaxis and exploratory behavior. Sensory neurons are denoted as triangles, interneurons as hexagons, and motor neurons as circles. Blue neurons stimulate turning; red neurons inhibit turning; black neurons have mixed activity; gray neurons are untested (Gray et al., 2005). Black lines indicate excitatory (arrow) and inhibitory (stopped) synapses or synaptic inputs established by calcium imaging (Chalasani et al., 2007; Macosko et al., 2009). Dashed lines indicate sites of neuromodulation (Zhang et al., 2005; Tsunozaki et al., 2008). Gray arrows indicate anatomically predicted, but functionally unconfirmed connections from the wiring diagram (White et al., 1986).

Calcium imaging experiments indicate that AWC and ASK sensory neurons detect changes in odor or food levels. AWC and ASK neurons are tonically active at rest and hyperpolarized by chemical stimuli: AWC is inhibited by specific odors or bacterially conditioned medium, and ASK is inhibited by pheromones or amino acids (Chalasani et al., 2007; Macosko et al., 2009; Wakabayashi et al., 2009). Both AWC and ASK are strongly activated if these chemical cues are removed, consistent with the evidence that they stimulate turning behavior following the removal of food.

AWC and ASK synapse onto a layer of interneurons that are also connected with each other, AIA, AIB, AIY, and AIZ. Cell ablations indicate that these interneurons coordinately control multiple classes of turning behaviors,including reversals and a sharp turn called an omega turn (Gray et al., 2005). AWC neurons are glutamatergic (Chalasani et al., 2007). AWC releases glutamate to activate AIB neurons through AMPA-type glutamate receptors, and it inhibits AIY neurons through glutamate-gated chloride channels. As a result, AIB is active upon odor removal, like AWC, whereas AIY becomes active upon odor addition. This circuitry can produce a coordinated switch in turning behavior. When food odors are present, AWC is inhibited, AIB is inactive, and AIY is tonically active; tonically active AIY suppresses turning. When food odors are removed, AWC becomes active, AIB becomes active and stimulates turning, and AIY is inhibited.

A second layer of interneurons and downstream motor neurons regulate specific classes of turns and features of turns (Gray et al., 2005). The AVA interneurons are backward command neurons; they are required for all kinds of reversals, including those triggered by the turning circuit, but they are not required for sharp omega turns. AVA synapses onto motor neurons in the body that drive backward locomotion. Conversely, the SMD and RIV motor neurons stimulate omega turns but are not required for reversals. SMD affects the steepness of the omega turn, while RIV biases omega turns toward the ventral side of the animal. Other neurons may affect gentler turns, including the SMB motor neurons that affect the amplitude of sinusoidal movement. The motor neurons in the turning circuit are largely cholinergic. The transmitters for most interneurons are unknown.

The same circuit that generates innate odor responses allows context and experience to modify odor preferences. Neuromodulatory inputs to interneurons or sensory neurons can reorganize the turning circuit to transform behavior. For example, C. elegans is susceptible to infection by common pathogenic bacteria, and it uses behavioral strategies as part of its antibacterial defense. Infection induces specific olfactory avoidance of pathogenic bacteria, a behavior that may be analogous to conditioned taste aversion (Zhang et al., 2005). Aversive odor learning requires serotonin, which promotes learning in many animals. Infection elevates serotonin, and exogenous serotonin accelerates learning, suggesting that serotonin provides an instructive learning signal. Serotonin converges on the turning circuit by activating the inhibitory serotonin receptor mod-1 on AIY and AIB interneurons.

Another form of plasticity in the turning circuit affects sensory neurons. One of the two AWC olfactory neurons, AWCON, can direct either attraction or repulsion depending on the experience of the animal. In naïve animals, odors sensed by AWCON are attractive, but extended starvation in the presence of these odors switches AWCON to repulsion (Tsunozaki et al., 2008). Three signaling molecules that regulate the switch between attraction and repulsion—a receptor-like guanylate cyclase (GCY-28, Fig. 51.1), a diacylglycerol kinase, and a protein kinase C homolog—all act in AWCON, apparently to modulate presynaptic release. These results suggest that alternative modes of neurotransmission can couple one sensory neuron to opposite behavioral outputs.

The AIA, AIB, AIY, and AIZ interneurons in this circuit receive extensive synaptic input from other sensory neurons. Two of the best-characterized sensory inputs come from AFD and ASE neurons, which also regulate taxis behaviors (Fig. 51.2). AFD thermosensory neurons use a biased random walk to drive thermotaxis to a preferred temperature, a behavior that has a strong component of heat avoidance (Mori and Ohshima, 1995; Ryu and Samuel, 2002). AFD neurons are depolarized at warm temperatures to promote turning (Ramot et al., 2008). ASE neurons sense attractive salts and other water-soluble attractants. The left and right ASE neurons have different sensory properties: the ASER neuron is hyperpolarized by attractive salts, resembling AWC, and has the largest role in chemotaxis; the contralateral ASEL neuron is depolarized by attractive salts (Suzuki et al., 2008). Salt chemotaxis results from a combination of a biased random walk strategy and a directed turning strategy in salt gradients (Iino and Yoshida, 2009). The AIA/AIB/AIY/AIZ interneurons regulate both the biased random walk and directed turning to salts; AIZ has the largest role among the interneurons (Iino and Yoshida, 2009).

Figure 51–2. Convergent sensory inputs target a common set of interneurons. Sensory neurons are denoted as triangles and interneurons are denoted as hexagons. Sensory neurons and their connections are color-coded for ease of viewing. Arrows indicate chemical synapses defined by the wiring diagram, including excitatory and inhibitory synapses; H-bar indicates gap junctions (White et al., 1986). AFD neurons are depolarized by (repulsive) high temperatures; AWC neurons are hyperpolarized by attractive odors. ASE neurons are bilaterally asymmetric; attractive NaCl concentrations inhibit the ASER neuron and activate the ASEL neuron (Suzuki et al., 2008). The synaptic connections made by ASER and ASEL are similar to each other.

Figure 51–2.
Convergent sensory inputs target a common set of interneurons. Sensory neurons are denoted as triangles and interneurons are denoted as hexagons. Sensory neurons and their connections are color-coded for ease of viewing. Arrows indicate chemical synapses defined by the wiring diagram, including excitatory and inhibitory synapses; H-bar indicates gap junctions (White et al., 1986). AFD neurons are depolarized by (repulsive) high temperatures; AWC neurons are hyperpolarized by attractive odors. ASE neurons are bilaterally asymmetric; attractive NaCl concentrations inhibit the ASER neuron and activate the ASEL neuron (Suzuki et al., 2008). The synaptic connections made by ASER and ASEL are similar to each other.

The patterns of synaptic connections made by ASE and AWC are almost identical, suggesting a common circuit mechanism for these two kinds of chemotaxis (Fig. 51.2). AFD synaptic partners overlap with those of ASE and AWC, but the exact patterns differ; for example, AFD forms gap junctions rather than chemical synapses with AIB. The circuit-level effects of these differences in connectivity are not known. ASE, AWC, and AFD are also linked by synapses to each other, but as yet there is no clear functional correlate of these anatomical connections.

In addition to the synaptic inputs from sensory neurons described earlier, extrasynaptic inputs from mechanosensory dopaminergic neurons affect local search behavior (Hills et al., 2004). It is likely that the turning circuit is a common substrate for a variety of exploratory and taxis behaviors that are regulated by sensory inputs.

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