Dataset Information

Cross-modal modulation gates nociceptive inputs in Drosophila.

ABSTRACT: Animals' response to a stimulus in one sensory modality is usually influenced by other modalities.¹ One important type of multisensory integration is the cross-modal modulation, in which one sensory modality modulates (typically inhibits) another. Identification of the mechanisms underlying cross-modal modulations is crucial for understanding how sensory inputs shape animals' perception and for understanding sensory processing disorders.²^,³^,⁴ However, the synaptic and circuit mechanisms that underlie cross-modal modulation are poorly understood. This is due to the difficulty of separating cross-modal modulation from multisensory integrations in neurons that receive excitatory inputs from two or more sensory modalities⁵-in which case it is unclear what the modulating or modulated modality is. In this study, we report a unique system for studying cross-modal modulation by taking advantage of the genetic resources in Drosophila. We show that gentle mechanical stimuli inhibit nociceptive responses in Drosophila larvae. Low-threshold mechanosensory neurons inhibit a key second-order neuron in the nociceptive pathway through metabotropic GABA receptors on nociceptor synaptic terminals. Strikingly, this cross-modal inhibition is only effective when nociceptor inputs are weak, thus serving as a gating mechanism for filtering out weak nociceptive inputs. Our findings unveil a novel cross-modal gating mechanism for sensory pathways.

SUBMITTER: Pan G

PROVIDER: S-EPMC10089977 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cross-modal modulation gates nociceptive inputs in Drosophila.

Pan Geng G Li Ruonan R Xu Guozhong G Weng Shijun S Yang Xiong-Li XL Yang Limin L Ye Bing B

Current biology : CB 20230308 7

Animals' response to a stimulus in one sensory modality is usually influenced by other modalities.1 One important type of multisensory integration is the cross-modal modulation, in which one sensory modality modulates (typically inhibits) another. Identification of the mechanisms underlying cross-modal modulations is crucial for understanding how sensory inputs shape animals' perception and for understanding sensory processing disorders.2,3, ...[more]

PMID: 36893758

Similar Datasets

Project description:BackgroundAlthough a number of clinical and preclinical studies have demonstrated analgesic effects of cannabinoid treatments, there are also instances when cannabinoids have had no effect or even exacerbated pain. The observed pro-nociceptive effects appear to be due to cannabinoid-induced disinhibition of afferent synaptic input to nociceptive circuits. To better understand how cannabinoid-mediated plasticity can have both pro- and anti-nociceptive effects, we examined the possibility that cannabinoids differentially modulate nociceptive vs. non-nociceptive synapses onto a shared postsynaptic target. These experiments were carried out in the central nervous system (CNS) of the medicinal leech, in which it is possible to intracellularly record from presynaptic nociceptive (N-cell) or pressure-sensitive (P-cell) neurons and their shared postsynaptic targets.ResultsThe endocannabinoid 2-arachidonoyl glycerol (2AG) elicited significant long-lasting depression in nociceptive (N-cell) synapses. However, non-nociceptive (P-cell) synapses were potentiated following 2AG treatment. 2AG-induced potentiation of non-nociceptive synapses was blocked by the TRPV antagonist SB366791, suggesting involvement of the same TRPV-like receptor that has already been shown to mediate endocannabinoid-dependent depression in nociceptive inputs. Treatment with the GABA receptor antagonist bicuculline also blocked 2AG-induced potentiation, consistent with the idea that increased synaptic signaling was the result of endocannabinoid-mediated disinhibition. Interestingly, while bicuculline by itself increased non-nociceptive synaptic transmission, nociceptive synapses were depressed by this GABA receptor antagonist indicating that nociceptive synapses were actually excited by GABAergic input. Consistent with these observations, GABA application depolarized the nociceptive afferent and hyperpolarized the non-nociceptive afferent.ConclusionsThese findings show that endocannabinoids can differentially modulate nociceptive vs. non-nociceptive synapses and that GABAergic regulation of these synapses plays an important role in determining whether endocannabinoids have a potentiating or depressing effect.

Dataset Information

Cross-modal modulation gates nociceptive inputs in Drosophila.

Publications

Cross-modal modulation gates nociceptive inputs in Drosophila.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets