Serotonin differentially modulates Ca2+ transients and depolarization in a C. elegans nociceptor.

Monoamines and neuropeptides modulate neuronal excitability and synaptic strengths, shaping circuit activity to optimize behavioral output. In C. elegans, a pair of bipolar polymodal nociceptors, the ASHs, sense I -octanol to initiate escape responses. in the present study, 1-octanol stimulated large increases in ASH Ca2+, mediated by L-type voltage-gated Ca2+ channels (VGCCs.) in the cell soma and L-plus P/Q-type VGCCs in the axon, which were further amplified by Ca2+ released from intracellular stores. Importantly, 1 -octanol-dependent aversive responses were not inhibited by reducing ASH L-VGCC activity genetically or pharmacologically. Serotonin, an enhancer of 1 -octanol avoidance, potentiated 1 -octanol-dependent ASH depolarization measured electrophysiologically, but surprisingly, decreased the ASH somal Ca2+ transients. These results suggest that ASH somal Ca2+ transient amplitudes may not always be predictive of neuronal depolarization and synaptic output. Therefore, although increases in steady-state Ca2+ can reliably indicate when neurons become active, quantitative relationships between Ca2+ transient amplitudes and neuronal activity may not be as straightforward as previously anticipated.