Experience-dependent reconfiguration of thermoreceptors regulates neuronal response plasticity

Neurons continuously adjust their properties as a function of experience. Precise modulation of neuronal responses is achieved by multiple cellular mechanisms that operate over a range of timescales. Primary sensory neurons not only rapidly adapt their sensitivities via posttranslational mechanisms, including regulated trafficking of sensory molecules,^1,2,3,4 but also alter their transcriptional profiles on longer timescales to adapt to persistent sensory stimuli.^5,6,7,8 How diverse transcriptional and posttranscriptional pathways are coordinated in individual sensory neurons to accurately adjust their functions and drive behavioral plasticity is unclear. Here, we show that temperature experience modulates both transcription and trafficking of thermoreceptors on different timescales in the C. elegans AFD thermosensory neurons to regulate response plasticity. Expression of the PY motif-containing adaptor protein (PY motif transmembrane 1 [PYT-1]), as well as the GCY-18 warm temperature-responsive guanylyl cyclase thermoreceptor,⁹ is transcriptionally upregulated in AFD upon a temperature upshift.^5,10 We find that as GCY-18 begins to accumulate at the AFD sensory endings, the GCY-23 cooler temperature-responsive thermoreceptor⁹ exhibits altered subcellular localization and increased retrograde trafficking, thereby increasing the functional GCY-18 to GCY-23 ratio in the AFD sensory compartment. Altered GCY-23 localization and trafficking require PYT-1-dependent endocytosis, and we show that PYT-1-mediated modulation of the GCY-18 to GCY-23 protein ratio at the AFD sensory endings is necessary to shift the AFD response threshold toward warmer values following the temperature upshift. Our results describe a mechanism by which transcriptional and posttranscriptional mechanisms are temporally coordinated across sensory receptors to fine-tune experience-dependent plasticity in the response of a single sensory neuron type.