Off-response in ASH neurons evoked by CuSO4 requires the TRP channel OSM-9 in Caenorhabditis elegans.

The off-response of ASH neurons had been overlooked until the microfluidic devices were introduced for in vivo imaging of neuronal activity in Caenorhabditis elegans. The mechanisms of ASH off-response were completely unknown. Here we monitored ASH off-response to CuSO4 stimulation by use of microfluidic device and genetically encoded calcium indicator (GECI) - Case12. We found ASH neurons exhibited a multiphasic response to 10 mM and 50 mM CuSO4 of 30-s stimulation duration. ASH off-responding to Cu(2+) had been dramatically reduced in goa-1, mod-5, trpa-1 and egl-8 mutants. Moreover, in osm-9 mutants ASH off-response was completely eliminated. Neuron-specific rescue of osm-9 in ASH neurons restored the off-response and the normal avoidance behavior in worms.

Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception and avoidance in Caenorhabditis elegans.

Sensory modulation is essential for animal sensations, behaviours and survival. Peripheral modulations of nociceptive sensations and aversive behaviours are poorly understood. Here we identify a biased cross-inhibitory neural circuit between ASH and ASI sensory neurons. This inhibition is essential to drive normal adaptive avoidance of a CuSO4 (Cu(2+)) challenge in Caenorhabditis elegans. In the circuit, ASHs respond to Cu(2+) robustly and suppress ASIs via electro-synaptically exciting octopaminergic RIC interneurons, which release octopamine (OA), and neuroendocrinally inhibit ASI by acting on the SER-3 receptor. In addition, ASIs sense Cu(2+) and permit a rapid onset of Cu(2+)-evoked responses in Cu(2+)-sensitive ADF neurons via neuropeptides possibly, to inhibit ASHs. ADFs function as interneurons to mediate ASI inhibition of ASHs by releasing serotonin (5-HT) that binds with the SER-5 receptor on ASHs. This elaborate modulation among sensory neurons via reciprocal inhibition fine-tunes the nociception and avoidance behaviour.