Abstract
Understanding neural functions inevitably involves arguments traversing multiple levels of hierarchy in biological systems. However, finding new components or mechanisms of such systems is extremely time-consuming due to the low efficiency of currently available functional screening techniques. To overcome such obstacles, we utilize pan-neuronal calcium imaging to broadly screen the activity of the C. elegans nervous system in response to thermal stimuli. A single pass of the screening procedure can identify much of the previously reported thermosensory circuitry as well as identify several unreported thermosensory neurons. Among the newly discovered neural functions, we investigated in detail the role of the AWCOFF neuron in thermal nociception. Combining functional calcium imaging and behavioral assays, we show that AWCOFF is essential for avoidance behavior following noxious heat stimulation by modifying the forward-to-reversal behavioral transition rate. We also show that the AWCOFF signals adapt to repeated noxious thermal stimuli and quantify the corresponding behavioral adaptation.
Highlights
C. elegans is one of the simplest multicellular organisms with only 302 neurons in hermaphrodites
By combining pan-neuronal calcium imaging with our novel behavioral analyses, we found that the AWCOFF neuron is essential and sufficient for noxious heat sensation and the subsequent avoidance behavior
Pan-neuronal calcium imaging coupled with thermal perturbations reveals novel neural functions
Summary
C. elegans is one of the simplest multicellular organisms with only 302 neurons in hermaphrodites. In the neuroscience of C. elegans, the most common approach to study neural functions is to apply a perturbation at the genetic or cellular level through techniques such as mutation, cell-ablation, or optogenetic stimulation, and screen the worm at the behavioral level. The general difficulty in making connections between these different hierarchies has hindered our ability to elucidate neural mechanisms connecting genes to behavior in C. elegans despite its extreme simplicity. It would be advantageous if we could directly screen for the neural functions in C. elegans, because we could apply perturbations and interpret the results all within one hierarchical level. We have taken an integrated approach and developed a pan-neuronal functional
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