Dissecting The Neural Circuit Underlying Robust And Flexible Motor Sequence Generation During Caenorhabditis Elegans Escape Responses

Rich and organized animal behaviors arise from a flexible combination of stereotyped motor primitives.How nervous systems generate interesting dynamics to purposefully explore the action space remains elusive.We use the nematode Caenorhabditis elegans as the model organism to investigate the neural circuit mechanisms for generating robust and flexible animal movements.We study the escape responses of C.elegans,which predictably moves away from a potential threat,such as a mechanical or thermal stimulus.Although the escape response has a stereotyped component(e.g.,backward locomotion,Omega turn),the motor sequences and the timing that constitute the whole behavior are variable.Our combined imaging,optogenetic and computational analyses suggest that a rapid feedforward pathway embedded in a stochastic recurrent attractor network underlies robust motor sequence generation,whereas functionally segregated neurons exploit synaptic inhibition with short-term depression to flexibly control motor state transitions.A feedback inhibition circuit between different motor modules has been found to terminate current motor state and to promote motor state transitons.Worm connectome and molecular genetics also reveal that the feedforward pathway uses electrical synapses to couple interneurons(eg.AIB)and motor neurons(eg.RIV,SMD)while lateral inhibition between local interneurons uses glutamate neurotransmitter as well as a class of glutamate-gated chloride channels.Together,we identify important circuit motifs and algorithms for stereotyped and flexible motor control in a numerically compact nervous system.These results have potentially laid a solid foundation for understanding sensorimotor transformation in larger animals,and will inspire the design of next generation of brain-like machines.