The transcription factor unc-130/FOXD3/4 contributes to the biphasic calcium response required to optimize avoidance behavior

Sayaka Hori,Shohei Mitani

doi:10.1038/s41598-022-05942-0

Abstract

The central neural network optimizes avoidance behavior depending on the nociceptive stimulation intensity and is essential for survival. How the property of hub neurons that enables the selection of behaviors is genetically defined is not well understood. We show that the transcription factor unc-130, a human FOXD3/4 ortholog, is required to optimize avoidance behavior depending on stimulus strength in Caenorhabditis elegans. unc-130 is necessary for both ON responses (calcium decreases) and OFF responses (calcium increases) in AIBs, central neurons of avoidance optimization. Ablation of predicted upstream inhibitory neurons reduces the frequency of turn behavior, suggesting that optimization needs both calcium responses. At the molecular level, unc-130 upregulates the expression of at least three genes: nca-2, a homolog of the vertebrate cation leak channel NALCN; glr-1, an AMPA-type glutamate receptor; and eat-4, a hypothetical L-glutamate transmembrane transporter in the central neurons of optimization. unc-130 shows more limited regulation in optimizing behavior than an atonal homolog lin-32, and unc-130 and lin-32 appear to act in parallel molecular pathways. Our findings suggest that unc-130 is required for the establishment of some AIB identities to optimize avoidance behavior.

Highlights

The central neural network optimizes avoidance behavior depending on the nociceptive stimulation intensity and is essential for survival
We report that unc-130 upregulates three genes: the putative Nematode CAlcium channel 219, a homolog of the vertebrate cation leak channel NALCN; AMPA-type glutamate receptor 120,21; and eat-4, a hypothetical L-glutamate transmembrane transporter[22]
C. elegans tends to show reversal behavior in response to mild osmolarity changes but is biased toward omega turns in a manner correlating with stimulus strength (Fig. 1a)[6]

Summary

Introduction

The central neural network optimizes avoidance behavior depending on the nociceptive stimulation intensity and is essential for survival. We show that the transcription factor unc[130], a human FOXD3/4 ortholog, is required to optimize avoidance behavior depending on stimulus strength in Caenorhabditis elegans. The excitation levels of the Mautner cells vary in response to stimulus intensity, but their association with behavioral changes remains unclear. We reported that C. elegans primarily uses three types of avoidance behaviors depending on the stimulus intensity: short reversals, long reversals, and omega turns[6]. We aimed to reveal a simple prototypical neural circuit at the synaptic level that optimizes avoidance behavior in C. elegans by using a complete neural wiring d iagram[7,8] and genes with human orthologs in O rthoList[9,10].

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