Serotonin disinhibits a caenorhabditis elegans sensory neuron by suppressing Ca2+-dependent negative feedback

Abstract

Neuromodulators, such as serotonin (5-HT), alter neuronal excitability and synaptic strengths, and define different behavioral states. Neuromodulator-dependent changes in neuronal activity patterns are frequently measured using calcium reporters because calcium imaging can easily be performed on intact functioning nervous systems. With only 302 neurons, the nematode Caenorhabditis elegans provides a relatively simple, yet powerful, system to understand neuromodulation at the level of individual neurons. C. elegans hermaphrodites are repelled by 1-octanol, and the initiation of these aversive responses is potentiated by 5-HT. 5-HT acts on the ASH polymodal nociceptors that sense the 1-octanol stimulus. Surprisingly, 5-HT suppresses ASH Ca2+ transients while simultaneously potentiating 1-octanol-dependent ASH depolarization. Here we further explore this seemingly inverse relationship. Our results show the following (1) 5-HT acts downstream of depolarization, through Gαq-mediated signaling and calcineurin, to inhibit L-type voltage-gated Ca2+ channels; (2) the 1-octanol-evoked Ca2+ transients in ASHs inhibit depolarization; and (3) the Ca2+-activated K+ channel, SLO-1, acts downstreamof5-HTandisacritical regulator of ASH responsedynamics. The sefindings definea Ca2+-dependentinhibitory feedback loop that can be modulated by 5-HT to increase neuronal excitability and regulate behavior, and highlight the possibility that neuromodulator-induced changes in the amplitudes of Ca2+transients do not necessarily predict corresponding changes in depolarization.