Positive interaction between ASH and ASK sensory neurons accelerates nociception and inhibits behavioral adaptation

Disexcitation in the ASH/RIM/ADL negative feedback circuit fine-tunes hyperosmotic sensation and avoidance in Caenorhabditis elegans

“…It hydrolyzes synaptobrevin and blocks vesicle fusion with the plasma membrane and, thus, synaptic transmission ( Schiavo et al, 1992 ). It is used to successfully eliminate neurotransmission in tested neurons (neurons:: TeTx in short; Macosko et al, 2009 ; Guo et al, 2015 ; Liu et al, 2019 ; Wen et al, 2020 ; Wu et al, 2022 ). In the test, the M13 buffer and different solutions of varied osmolality were used as a control and stimuli, respectively.…”

“…Given that ADL regulates hyperosmotic avoidance, it should respond to hyperosmotic stimulation cell-or non-cell-autonomously. We thus examined ADL calcium (Ca 2+ ) responses to the medium hyperosmolality of 0.88 Osm by 0.5 M glycerol/M13 solution, using fluorescent Ca 2+ imaging with GCaMP3.0 as a Ca 2+ indicator ( Tian et al, 2009 ) combined with microfluidic control of stimulation and animal movement ( Chronis et al, 2007 ; Guo et al, 2015 ; Wang et al, 2015 ; Liu et al, 2019 ; Ge et al, 2020 ; Wen et al, 2020 ; Wu et al, 2022 ). ADL neurons in the WT N2 worm displayed robust Ca 2+ responses to 0.88 Osm osmolality ( Figures 1B , C ; Supplementary Figure S1E ).…”

“…All experiments were performed using synchronized young adult animals maintained on 6 cm nematode growth medium (NGM) plates and at 20°C. The hyperosmotic shock test was performed using a wet-drop test for assaying avoidance of acute hyperosmotic simulation, as previously described ( Hilliard et al, 2004 ; Guo et al, 2015 ; Krzyzanowski et al, 2016 ; Wu et al, 2022 ). Briefly, 10 or more young adults were transferred onto NGM plates without food, OP50 bacteria lawn, and let freely move to remove bacteria.…”

“…Animals regularly encounter, sense, and avoid noxious environmental stimuli, such as hyperosmotic and hypoosmotic stress ( Culotti and Russell, 1978 ; Hilliard et al, 2005 ), excessive mechanical forces ( Walker et al, 2009 ; Campbell et al, 2015 ), aversive smells ( Li and Liberles, 2015 ; Duan et al, 2020 ), heavy metal ions ( Sambongi et al, 1999 ; Guo et al, 2015 ; Wu et al, 2022 ), harmful pH ( Sambongi et al, 2000 ; Spalthoff and Gopfert, 2016 ), alkaloids quinine ( Hilliard et al, 2004 ; Voelker et al, 2019 ), extreme temperatures ( Takeishi et al, 2020 ), etc. Environmental osmolality fluctuation is a universal challenge for organisms.…”

“…Nociception, the sense of nociceptive stimuli with actual or potential tissue injuries, produces a diverse set of sensations, pain perceptions, emotions, and actions, including behavioral responses. Primary nociception and its modulations at the level of sensory neurons or the initial chain of sensory pathways provide more veridical and instantaneous information for animals to achieve rapid, more fine-tuned, and concentrated behavioral responses ( Baliki and Apkarian, 2015 ; Guo et al, 2015 ; Liu et al, 2019 ; Wu et al, 2022 ). Peripheral circuitry modulations of nociception include: innocuous afferent fibers gating the transmission of nociceptive fibers via a relay of a peripheral inhibitory neuron as proposed by gate control theory ( Melzack and Wall, 1965 ), non-nociceptive ASI (Amphid Single Cilium I) neurons reciprocally inhibiting nociceptive ASH (Amphid Single Cilium H; Guo et al, 2015 ), and secondary nociceptive ASK (Amphid Single Cilium K) neurons suppressing ASH activities by providing cGMP through gap junctions in the nematode Caenorhabditis elegans ( C. elegans ; Voelker et al, 2019 ; Wu et al, 2022 ).…”