Feedforward and feedback mechanisms cooperatively regulate rapid experience-dependent response adaptation in a single...

Area of Science:

• Neuroscience
• Cell Biology
• Sensory Biology

Background:

• Sensory adaptation adjusts neuronal sensitivity to stimuli based on experience.
• Mechanisms for continuous adaptation over seconds to hours within single neuron types remain unclear.
• The AFD thermosensory neurons in *C. elegans* show experience-dependent plasticity in temperature response thresholds.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying rapid thermosensory response adaptation in AFD neurons.
• To investigate whether both transcriptional and nontranscriptional mechanisms contribute to adaptation within a single neuron type.

Main Methods:

• Investigated rapid adaptation in *C. elegans* AFD thermosensory neurons.
• Utilized genetic and molecular approaches to study cGMP and calcium signaling pathways.
• Examined the roles of thermosensor receptor guanylyl cyclases (rGCs) and downstream effectors.

Main Results:

• Rapid adaptation in AFD neurons is mediated by cGMP and calcium-dependent feedforward and feedback mechanisms.
• Either of the two rGCs is sufficient for rapid adaptation, with each operating at different rates.
• Adaptation involves phosphorylation of rGC intracellular domains and calcium-dependent regulation of cGMP levels.
• cGMP-dependent protein kinases phosphorylate the cGMP-gated channel subunit, further regulating adaptation.

Conclusions:

• Identified multiple molecular pathways, including cGMP and calcium signaling, for rapid adaptation in AFD thermosensory neurons.
• Demonstrated that both transcriptional and nontranscriptional mechanisms within a single neuron type contribute to continuous sensory adaptation.