A New Role Of RIM Neuron In Locomotion Regulation Of C.elegans

As a classic model system,Caenorhabditis elegans is widely used to study the machnisms of how neural circuits and genes generate behavior.During free moving locomotion,worms maintain forward movement for most time which is interrupted by spontaneous reversal,and the neurons involving in reversal initiation are required for movement direction change and avoidance behavior occurrence,however,the underlying neural mechanism are not well understood.As reported,AVA,AVD and AVE play important roles in reversal initiation in C.elegans,as the frequency of backward movement decrease significantly when those neurons are ablated.Command interneuron AVA receives signals from upstream neurons and modulates the motion state in real-time during navigation.Sensory neurons can directly activate AVA or transactive other interneurons(AIB,AIY,RIM)to drive backward locomotion,in which RIM neuron plays a key role in integrating external stimuli and backward locomotion initiation.While the function of RIM in reversal regulation is quite complicate,RIM inhibits AVB neuron by releasing tyramine to cease forward movement via synaptic connections and activates AVA to promote reversal through gap junction in avoidance behavior.Furthermore,ablation of RIM or inhibition of tyramine synthesis in RIM significantly increase the spontaneous reversal frequency,indicating that RIM could restrain reversal.To sum up,RIM neurons have a dual role in reversal regulation,which has never been well defined.So we focus on investigating the molecular mechanism of RIM regulating backward locomotion in free moving worms.From optogenetics and laser ablation studies,we affirmed the dual role of RIM on backward locomotion regulation.After activation,RIM performs an acute response: boosting reversal through gap junction composing of INX-1 expressed in RIM and UNC-7,UNC-9 expressed in AVA,AVE;then a chronic response shows up: glutamate released from RIM activates the chloride channel AVR-14,leading to AVA and AVE deactivation and reversal inhibition.The dual function of RIM can facilitate worms reacting to noxious clues potently and restore AVA to a resting state soon after activation,which protected motor neurons from injuring or desensitizing by long term excitation.AVR-14 was verified as a glutamate-gated chloride channel,which induce chloride ions influx and neuron hyperpolarization.The homologous gene has been found in drosophila and other nematode species,but not in mammals.Nowadays,the function of AVR-14 in physiological processes is barely documented.In general,we presented a novel molecular mechanism in RIM for reversal regulation,and revealed the new role of glutamate-gated chloride channel in locomotion neuron circuit,which provide important functions of inhibitory glutamate receptor.The discovery of inhibitory role of RIM uncovered the functions of glutamate in RIM and illustrated the complexity and multifunctionality of neuron network.