Neural substrates of cold nociception in Drosophila larva
Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus-specific behaviors to either navigate away from injury-causing conditions or to perfo...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/91582 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850102649036210176 |
|---|---|
| author | Atit A Patel Albert Cardona Daniel N Cox |
| author_facet | Atit A Patel Albert Cardona Daniel N Cox |
| author_sort | Atit A Patel |
| collection | DOAJ |
| description | Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus-specific behaviors to either navigate away from injury-causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Recent studies in Drosophila larvae have revealed that somatosensory class III multidendritic (CIII md) neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Recent advances in circuit bases of behavior have identified and functionally validated Drosophila larval somatosensory circuitry involved in innocuous (mechanical) and noxious (heat and mechanical) cues. However, central processing of cold nociceptive cues remained unexplored. We implicate multisensory integrators (Basins), premotor (Down-and-Back), and projection (A09e and TePns) neurons as neural substrates required for cold-evoked behavioral and calcium responses. Neural silencing of cell types downstream of CIII md neurons led to significant reductions in cold-evoked behaviors, and neural co-activation of CIII md neurons plus additional cell types facilitated larval contraction (CT) responses. Further, we demonstrate that optogenetic activation of CIII md neurons evokes calcium increases in these neurons. Finally, we characterize the premotor to motor neuron network underlying cold-evoked CT and delineate the muscular basis of CT response. Collectively, we demonstrate how Drosophila larvae process cold stimuli through functionally diverse somatosensory circuitry responsible for generating stimulus-specific behaviors. |
| format | Article |
| id | doaj-art-140c4dd80ec34a29a9080f8e995f41b8 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-140c4dd80ec34a29a9080f8e995f41b82025-08-20T02:39:43ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011210.7554/eLife.91582Neural substrates of cold nociception in Drosophila larvaAtit A Patel0https://orcid.org/0009-0007-7639-0518Albert Cardona1Daniel N Cox2https://orcid.org/0000-0001-9191-9212Neuroscience Institute, Georgia State University, Atlanta, United StatesHHMI Janelia Research Campus, Ashburn, United States; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom; MRC Laboratory of Molecular Biology, Cambridge, United KingdomNeuroscience Institute, Georgia State University, Atlanta, United States; School of Life Sciences, Arizona State University, Tempe, United StatesMetazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus-specific behaviors to either navigate away from injury-causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Recent studies in Drosophila larvae have revealed that somatosensory class III multidendritic (CIII md) neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Recent advances in circuit bases of behavior have identified and functionally validated Drosophila larval somatosensory circuitry involved in innocuous (mechanical) and noxious (heat and mechanical) cues. However, central processing of cold nociceptive cues remained unexplored. We implicate multisensory integrators (Basins), premotor (Down-and-Back), and projection (A09e and TePns) neurons as neural substrates required for cold-evoked behavioral and calcium responses. Neural silencing of cell types downstream of CIII md neurons led to significant reductions in cold-evoked behaviors, and neural co-activation of CIII md neurons plus additional cell types facilitated larval contraction (CT) responses. Further, we demonstrate that optogenetic activation of CIII md neurons evokes calcium increases in these neurons. Finally, we characterize the premotor to motor neuron network underlying cold-evoked CT and delineate the muscular basis of CT response. Collectively, we demonstrate how Drosophila larvae process cold stimuli through functionally diverse somatosensory circuitry responsible for generating stimulus-specific behaviors.https://elifesciences.org/articles/91582cold nociceptionthermosensationsomatosensory circuitsDrosophila |
| spellingShingle | Atit A Patel Albert Cardona Daniel N Cox Neural substrates of cold nociception in Drosophila larva eLife cold nociception thermosensation somatosensory circuits Drosophila |
| title | Neural substrates of cold nociception in Drosophila larva |
| title_full | Neural substrates of cold nociception in Drosophila larva |
| title_fullStr | Neural substrates of cold nociception in Drosophila larva |
| title_full_unstemmed | Neural substrates of cold nociception in Drosophila larva |
| title_short | Neural substrates of cold nociception in Drosophila larva |
| title_sort | neural substrates of cold nociception in drosophila larva |
| topic | cold nociception thermosensation somatosensory circuits Drosophila |
| url | https://elifesciences.org/articles/91582 |
| work_keys_str_mv | AT atitapatel neuralsubstratesofcoldnociceptionindrosophilalarva AT albertcardona neuralsubstratesofcoldnociceptionindrosophilalarva AT danielncox neuralsubstratesofcoldnociceptionindrosophilalarva |