Feedforward and feedback mechanisms cooperatively regulate rapid experience-dependent response adaptation in a single thermosensory neuron type

Abstract

Sensory adaptation allows neurons to adjust their sensitivity and responses based on recent experience. The mechanisms that mediate continuous adaptation to stimulus history over seconds to hours long timescales, and whether these mechanisms can operate within a single sensory neuron type, are unclear. The single pair of AFD thermosensory neurons in C. elegans exhibits experience-dependent plasticity in their temperature response thresholds on both minutes- and hours-long timescales upon a temperature upshift. While long-term response adaptation requires changes in gene expression in AFD, the mechanisms driving rapid response plasticity are unknown. Here, we show that rapid thermosensory response adaptation in AFD is mediated via cGMP and calcium-dependent feedforward and feedback mechanisms operating at the level of primary thermotransduction. We find that either of two thermosensor receptor guanylyl cyclases (rGCs) alone is sufficient to drive rapid adaptation, but that each rGC drives adaptation at different rates. rGC-driven adaptation is mediated in part via phosphorylation of their intracellular domains, and calcium-dependent feedback regulation of basal cGMP levels via a neuronal calcium sensor protein. In turn, cGMP levels feedforward via cGMP-dependent protein kinases to phosphorylate a specific subunit of the cGMP-gated thermotransduction channel to further regulate rapid adaptation. Our results identify multiple molecular pathways that act in AFD to ensure rapid adaptation to a temperature change, and indicate that the deployment of both transcriptional and non-transcriptional mechanisms within a single sensory neuron type can contribute to continuous sensory adaptation. Significance statementThe nervous system must continuously adapt to the sensory environment in order to adjust response sensitivity. Although both short- and long-term response adaptation has been reported to occur within sensory neurons themselves, how temporally distinct plasticity mechanisms are coordinated within single sensory neurons is unclear. We previously showed that long-term adaptation of temperature responses in the single AFD thermosensory neuron pair in C. elegans is mediated via gene expression changes in this neuron type. Here we show that multiple second messenger-driven feedforward and feedback mechanisms act to drive rapid thermosensory adaptation in AFD. Our results indicate that modulation of thermotransduction molecules via both transcriptional and non-transcriptional mechanisms contribute to distinct temporal phases of adaptation in a single sensory neuron type.