Nociceptive interneurons control modular motor pathways to promote escape behavior in Drosophila

Abstract

Rapid and efficient escape behaviors in response to noxious sensory stimuli are essential for protection and survival. Yet, how noxious stimuli are transformed to coordinated escape behaviors remains poorly understood. In Drosophila larvae, noxious stimuli trigger sequential body bending and corkscrew-like rolling behavior. We identified a population of interneurons in the nerve cord of Drosophila, termed Down-and-Back (DnB) neurons, that are activated by noxious heat, promote nociceptive behavior, and are required for robust escape responses to noxious stimuli. Electron microscopic circuit reconstruction shows that DnBs are targets of nociceptive and mechanosensory neurons, are directly presynaptic to pre-motor circuits, and link indirectly to Goro rolling command-like neurons. DnB activation promotes activity in Goro neurons, and coincident inactivation of Goro neurons prevents the rolling sequence but leaves intact body bending motor responses. Thus, activity from nociceptors to DnB interneurons coordinates modular elements of nociceptive escape behavior.

Integrins protect nociceptive neurons in models of paclitaxel-mediated peripheral sensory neuropathy

“…Larvae have a stereotyped behavioral response towards noxious stimuli that can serve as a readout of nociceptive neuron function (Burgos et al, 2018;Chen et al, 2016;Hwang et al, 2007;Poe et al, 2017). Nociceptive neurons in Drosophila larvae may therefore serve as a good in vivo model to study sensory changes induced by chemotherapeutics at morphological and functional levels.…”

“…Drosophila larvae show a stereotyped nocifensive behavior in response to thermal or mechanical noxious stimuli consisting of sequential C-shaped body bending, lateral rolling, and fast escape crawl (Burgos et al, 2018;Hwang et al, 2007;Ohyama et al, 2013;Tracey et al, 2003). We administered paclitaxel at 1, 10, and 20μM and tested for heat-induced nocifensive behavior.…”

“…Global activation heat nocifensive assays were performed as previously described (Burgos et al, 2018)…”

“…To determine if paclitaxel exerted an effect on sensory neurons or somewhere downstream of primary nociceptors, we performed a circuit epistasis experiment ( Supplementary Figure 4). We fed larvae paclitaxel and activated downstream circuitry by expressing TrpA in Down and back (DnB) neurons, one of the main downstream targets of larval nociceptive neurons (Burgos et al, 2018).…”

“…Thermogenetic activation of DnB neurons elicits bending and rolling behavior (Burgos et al, 2018), so we predicted that direct activation of DnB neurons would still be able to induce rolling behavior if the nociceptive neurons were the major target of paclitaxel. Indeed, activation of DnB neurons was as effective at inducing nociceptive behaviors with and without paclitaxel feeding.…”