The Molecular Mechanism Of Sensory Neurons ASI Modulate ADF In Nociceptive Sensation In C.elegans

Avoidance behavior is the most important behavior to survival.Avoidance behavior is the signal integration that happen at multi-levels.The model organism of Caenorhabditis elegans has been increasingly applied in the functional of stimulus-input and behavior-output,for its transparent body,short life-cycle and fewer neurons.In C.elegans,various and multi-staged neurons,including sensory neurons,interneurons and motor neurons,mediate the avoidance behavior.However,understanding sensory neurons modulation,especially underlying the molecular mechanism of neural circuit at peripheral level is still in its infancy.In C.elegans,ASI is a pair of cell body and multi-model sensory neuron,and has been reported to mediate various behaviors.Such as,modulating the dauer through daf-pathway;feedback regulating temperature via ion channels;modulating the exploratory behaviors,which consisting spontaneous backward and omega turns,and substituting for specific sensory neurons function after those neurons functional abnormal.ADF is also a pair multi-model sensory neuron,which releasing 5-HT,and functional different according to the level of 5-HT.It is reported that ASI promoted ADF activity during the CuSO4 stimulation,but unknown the underlying molecular mechanism.Thus,we use molecular techniques,quantitative behaviour,calcium imaging,optogenetics methods to study the molecular mechanism in ASI modulating ADF nociceptive sensation.The results suggesting that blocking ASI neurotransmission by espression of TeTx or inhibition of ASI activity by optogenetic method,ADF calcium transient displays an obvious delay.Throgh screening the participating peptide secretion of proprotein convertase lof mutants egl-3 and egl-21,we found that neuropeptide mediated the ASI inhibition of ADF.Finally,the conclusion is further demonstrated through quantitative behaviour experiments.Through the screening the neuropeptide lof mutants,we found that nlp-3 and ins-1 synergistic regulated ADF activity.