Dissectiong The Neuronal Circuit Of Flexible Motor Sequence Generation During Caenorhabditis Elegans Robust Escape Responses

Animals have robust and flexible motor control systems,which enable them to continuously execute variable and coordinated motor patterns to survive in a changing environment.A complex behavior is composed of a series of motor modules,constituting a robust and flexible motor sequence.How nervous systems perform flexible decision-making and execute the different motor processes in an orderly manner remain unknown.There are two prevailing views of neural control of sequential activities in the brain.In the first scheme,feedforward excitation in a synaptic chain would transiently activate different groups of neurons.In the second scheme,sequential neural activity could emerge from mutually inhibited neuron clusters through a winner-take-all strategy.Here,we investigate neural mechanisms for motor sequence generation in C.elegans with the aid of its connectome during escape responses.A mechanosensory or thermosensory stimulation at a worm's head can reliably trigger a robust escape response.The escape response is driven by three conservative motor modules:backward module,forward module and turning module.By combining optogenetic and calcium imaging technologies in vivo,we found that this rudimentary motor sequence is controlled by a neural circuit that combines the above two schemes.In particular,feedforward excitation is contributed by electrical couplings between interneurons AIB,which encode the backward motor state,and RIV in the turning module.RIB in the forward/turning module modulate turning module;and a feedback inhibition motif from SAAD in the turning module onto interneurons in the backward module,which contribute to reversal termination during type-? transition.Remarkably,when neurons in the turning module were ablated,leading to prolonged reversals with an exponential dwell time distribution.In other words,feedback inhibition from the turning module plays a critical role in terminating persistent activity in the backward module.Together,our data suggest that feedforward excitation and selective inhibitions between neuron groups contribute to robust and flexible motor sequence generation in C.elegans.Similar strategies could be applied to higher creatures and further inspire the design of brain-like machines.