Neuronal and genetic basis of a novel episodic behavior in Caenorhabditis elegans

Abstract

Episodic rhythmic behaviors stop, remain in quiescence, and restart. This stopping and restarting and the nature of the quiescent phase has been relatively less well explored than the mechanism of rhythm generation itself. This thesis reports a novel paradigm in C. elegans locomotion in liquid to probe into the episodic nature of a behavior. In a liquid medium a worm stops and restarts, alternating between swimming (S) and quiescent (Q) states. After an initial swim bout, worms oscillate between periods of S, lasting about 12 min, and periods of Q, lasting 5 min +/- 1 min. This study shows that motion appeared to stop due to an excess of cholinergic signaling at the neuromuscular junction, which presumably results in tonic muscle contractions. Development of this condition was strongly influenced by the activities of command inter-neurons that regulate the system of cholinergic motor neurons. This study identified the command inter-neurons required for the S to Q as well as the Q to S switch. Likewise, sensory input acting through the command inter-neurons affected the pattern of swim and quiescence. The observations do not appear to require a central pattern generator outside the motor circuitry to drive the locomotory circuit.;A candidate gene approach revealed that the protein kinase G homolog, egl-4, significantly reduces Q duration. Thus if Q was due to excess cholinergic signaling, egl-4 is required for promoting cholinergic signaling. Mutations in cnb-1/tax-6, a calcineurin phosphatase homolog, resulted in abnormal S-Q switching with the phosphatase apparently promoting S. Analysis of genetic interaction between egl-4 and tax-6 provided evidence that they oppose each other in maintaining swimming. The results and observations reported in this thesis establish C. elegans as a system for studying episodic rhythmic behavior at the neuronal and genetic level. The study of this behavior is consistent with the hypothesis that in an episodic behavior the brake on rhythmic motor activity may lie within the network that generates the rhythm.