Neural Circuitry that Evokes Escape Behavior upon Activation of Nociceptive Sensory Neurons in Drosophila Larvae

Abstract

Noxious stimuli trigger a stereotyped escape response in animals. In Drosophila larvae, class IV dendrite arborization (C4 da) sensory neurons in the peripheral nervous system are responsible for perception of multiple nociceptive modalities, including noxious heat and harsh mechanical stimulation, through distinct receptors [1-9]. Silencing or ablation of C4 da neurons largely eliminates larval responses to noxious stimuli [10-12], whereas optogenetic activation of C4 da neurons is sufficient to provoke corkscrew-like rolling behavior similar to what is observed when larvae receive noxious stimuli, such as high temperature or harsh mechanical stimulation [10-12]. The receptors and the regulatory mechanisms for C4 da activation in response to a variety of noxious stimuli have been well studied [13-23], yet how C4 da activation triggers the escape behavior in the circuit level is still incompletely understood. Here we identify segmentally arrayed local interneurons (medial clusters of C4 da second-order interneurons [mCSIs]) in the ventral nerve cord that are necessary and sufficient to trigger rolling behavior. GFP reconstitution across synaptic partners (GRASP) analysis indicates that C4 da axons form synapses with mCSI dendrites. Optogenetic activation of mCSIs induces the rolling behavior, whereas silencing mCSIs reduces the probability of rolling behavior upon C4 da activation. Further anatomical and functional studies suggest that the C4 da-mCSI nociceptive circuit evokes rolling behavior at least in part through segmental nerve a (SNa) motor neurons. Our findings thus uncover a local circuit that promotes escape behavior upon noxious stimuli in Drosophila larvae and provide mechanistic insights into how noxious stimuli are transduced into the stereotyped escape behavior in the circuit level.

Drosophila melanogaster foraging regulates a nociceptive-like escape behavior through a developmentally plastic sensory circuit

“…The cIV multidendritic neurons are known to synapse onto the ventral region of the ventral nerve cord (VNC) (19,(45)(46)(47). We next tested whether pr1 VNC neurons were required for the curling and rolling response by genetically separating pr1-GAL4 brain lobe expression from VNC expression by combining the VNC-specific GAL4 inhibitor tsh-GAL80 (48) with pr1-GAL4.…”

ADrosophilalarval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity

“…Neurotransmitter expression has been characterized for only a small fraction of the PMNs described here (Kohsaka et al 2014; Heckscher et al 2015; Fushiki et al 2016; Hasegawa et al 2016; MacNamee et al 2016; Zwart et al 2016; Takagi et al 2017; Yoshino et al 2017; Burgos et al 2018; Carreira-Rosario et al 2018). To increase coverage, we screened for Gal4 lines with sparse expression patterns, performed MultiColorFlpOut (Nern et al 2015) to match their morphology to individual PMNs, and mapped neurotransmitter expression.…”

Drosophilamodel of Anti-retroviral therapy Induced Peripheral Neuropathy and Nociceptive Hypersensitivity

“…Drosophila larval model has been previously used in understanding the mechanisms of nociception 32,33,[43][44][45] . When subjected to noxious stimuli, like high temperatures, the larvae respond by a characteristic "corkscrew-like" escape behavior, also called as writhe 46 , which has been successfully exploited to screen for genes involved in nociception 34,47,48 . Larvae that are sensitive to these noxious stimuli generally respond with writhe at a lower threshold than the control larvae.…”