The TRPA1 Ion Channel Contributes to Sensory-Guided Avoidance of Menthol in Mice

Lemon, Christian H.; Norris, Jordan E.; Heldmann, Bradley A.

doi:10.1523/eneuro.0304-19.2019

Cited by 23 publications

(24 citation statements)

References 49 publications

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“…We also found that application of HC-030031 has weaker inhibitory effects on dTRPA1 currents than previously reported for mammalian isoforms [61]. This is consistent with HC-030031 having species-dependent effects, inhibiting the human, In regard to menthol, the well-documented activation of mouse TRPA1 induced by this compound [31,33] can readily explain the implication of this channel in the aversive behavior of mice to menthol in a drinking assay [52]. In contrast, the scenario in Drosophila is not so clear, as the precise role of dTRPA1 in menthol-induced aversion during oviposition [40] and nocifensive responses of larvae towards direct contact [34] remained unexplored.…”

Section: Discussionsupporting

confidence: 89%

Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol

Boonen

Startek

Milici

et al. 2021

IJMS

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Background: The transient receptor potential ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca2+ imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in dTrpA1 mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) > dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) > dTRPA1(D) > dTRPA1(C) > dTRPA1(B) for menthol. Conclusions: dTrpA1 was required for the normal avoidance of Drosophila melanogaster towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels.

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Section: Discussionsupporting

confidence: 89%

Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol

Boonen

Startek

Milici

et al. 2021

IJMS

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“…In regard to menthol, the well-documented activation of mouse TRPA1 induced by this compound [25,27] can readily explain the implication of this channel in the aversive behavior of mice to menthol in a drinking assay [47]. In contrast, the scenario in Drosophila is not so clear, since the precise role of dTRPA1 in menthol-induced aversion during oviposition [39] and nocifensive responses of larvae towards direct contact [28] remained unexplored.…”

Section: Discussionmentioning

confidence: 99%

Activation of<em> Drosophila melanogaster</em> TRPA1 isoforms by citronellal and menthol

Boonen¹,

Startek²,

Milici³

et al. 2021

Preprint

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The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca2+ imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in dTrpA1 mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) &gt; dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) &gt; dTRPA1(D) &gt; dTRPA1(C) &gt; dTRPA1(B) for menthol. Conclusions: dTrpA1 was required for the normal avoidance of Drosophila melanogaster towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels.

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“…The tested concentration of menthol stimulates lingual trigeminal fibers (Lundy and Contreras, 1995) and its oral sensation is not avoided by mice. In an orosensory setting, wild-type mice show only a mild reduction in licking 1.28 mM menthol compared to water (Lemon et al, 2019).…”

Section: Optical and Electrical Stimulimentioning

confidence: 97%

“…AITC engages nociceptors expressing TRP ankyrin 1 (TRPA1) and stimulates TRPV1 at high concentrations (Jordt et al, 2004;Everaerts et al, 2011). Whereas 0.1 mM AITC causes a moderate reduction in licking compared to water in mouse orosensory tests, 1 mM AITC elicits near-zero licks and strong aversion (Lemon et al, 2019).…”

Section: Optical and Electrical Stimulimentioning

confidence: 99%

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TRPV1-lineage somatosensory fibers communicate with taste neurons in the mouse parabrachial nucleus

Ali

Lemon

2021

Preprint

Self Cite

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Trigeminal neurons supply somatosensation to craniofacial tissues. In mouse brain, ascending projections from medullary trigeminal neurons arrive at taste neurons in the autonomic parabrachial nucleus, suggesting taste neurons participate in somatosensory processing. However, the genetic cell types that support this convergence were undefined. Using Cre-directed optogenetics and in vivo neurophysiology in anesthetized mice of both sexes, here we studied whether TRPV1-lineage nociceptive and thermosensory fibers are primary neurons that drive trigeminal circuits reaching parabrachial taste cells. We monitored spiking activity in individual parabrachial neurons during photoexcitation of the terminals of TRPV1-lineage fibers that arrived at the dorsal spinal trigeminal nucleus pars caudalis, which relays orofacial somatosensory messages to the parabrachial area. Parabrachial neural responses to oral delivery of taste, chemesthetic, and thermal stimuli were also recorded. We found that optical excitation of TRPV1-lineage fibers frequently stimulated traditionally defined taste neurons in lateral parabrachial nuclei. The tuning of neurons across diverse tastes associated with their sensitivity to excitation of TRPV1-lineage fibers, which only sparingly engaged neurons oriented to preferred tastes like sucrose. Moreover, neurons that responded to photostimulation of TRPV1-lineage afferents showed strong responses to temperature including noxious heat, which predominantly excited parabrachial bitter taste cells. Multivariate analyses revealed the parabrachial confluence of TRPV1-lineage signals with taste captured sensory valence information shared across aversive gustatory, nociceptive, and thermal stimuli. Our results reveal that trigeminal fibers with defined roles in thermosensation and pain communicate with parabrachial taste neurons. This multisensory convergence supports dependencies between gustatory and somatosensory hedonic representations in the brain.

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The TRPA1 Ion Channel Contributes to Sensory-Guided Avoidance of Menthol in Mice

Abstract: Visual Abstract

Cited by 23 publications

References 49 publications

Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol

Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol

Activation of<em> Drosophila melanogaster</em> TRPA1 isoforms by citronellal and menthol

TRPV1-lineage somatosensory fibers communicate with taste neurons in the mouse parabrachial nucleus

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