The Neural Circuit Mechanism Of Transition Between Backward And Turning Modules In Caenorhabditis Elegans

Complex motor behavior is composed of a series of motor modules that are organized in an ordered and flexible combination.Coordinated transition between these motor modules is the basis for behavior decision making.The neural circuit mechanisms that shape the dynamics of motor module transitions remain poorly understood.The prevailing view on generating sequential movements is the synaptic chain model that relies on feedforward excitation.When C.elegans perceives dangerous stimuli,it will generate an escape response that consists of three conservative motor modules:backward movement,turn,and forward locomotion.It is critical that the backward movement ends at the right time and changes into an omega turn.Here,by combining behavior tracking,optogenetics,in vivo calcium imaging and molecular genetics,we investigated the neural circuit mechanisms underlying backward-turn transitions during C.elegans escape response.We found that RIV motor neurons and their downstream neurons SAA/SMB participate in an inhibitory regulation of backward movement through chemical synapses,thereby promoting reversal termination.Since SAA are cholinergic neurons,we analyzed C.elegans locomotion in putative acetylcholine-gated chloride channel subunit deficient mutants(acc-1,acc-2,acc-3,acc-4),and found that the long timescale behavioral dynamics that characterize the transitions between motor states are altered in these mutants.We found that all these four receptor genes exhibit expression in RIM,an integrating interneuron that plays a central role in motor state transitions,and the ablation of RIM affected the regulation of reversal termination by RIV/SAA/SMB neurons.Finally,we found that RIV motor neurons and SAA/SMB neurons inhibit RIM interneuron through acetylcholine-gated chloride channel receptors,thereby terminating the reversal and ensuring the normal initiation of turn.In conclusion,our study suggests that the reversal-turn motor transition in C.elegans is modulated by feedback inhibition from neurons in the turning module to the neuron in the backward module,and this inhibition is mediated through acetylcholine and its inhibitory receptors.Our experimental results reveal a simple mechanism for motor state transition at the neural circuit level,and may find general applications for motor sequence generation in higher organisms.