Dataset Information

Molecular Logic of Synaptic Diversity Between Drosophila Tonic and Phasic Motoneurons.

ABSTRACT: Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features is poorly understood. To identify molecular pathways that contribute to synaptic diversity, single neuron PatchSeq RNA profiling was performed on Drosophila tonic and phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while phasic motoneurons form stronger depressing synapses onto multiple muscles. Super-resolution microscopy and in vivo imaging demonstrated synaptic active zones in phasic motoneurons are more compact and display enhanced Ca ²⁺ influx compared to their tonic counterparts. Genetic analysis identified unique synaptic properties that mapped onto gene expression differences for several cellular pathways, including distinct signaling ligands, post-translational modifications and intracellular Ca ²⁺ buffers. These findings provide insights into how unique transcriptomes drive functional and morphological differences between neuronal subtypes.

SUBMITTER: Jetti SK

PROVIDER: S-EPMC9882338 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Molecular Logic of Synaptic Diversity Between <i>Drosophila</i> Tonic and Phasic Motoneurons.

Jetti Suresh K SK Crane Andrés B AB Akbergenova Yulia Y Aponte-Santiago Nicole A NA Cunningham Karen L KL Whittaker Charles A CA Littleton J Troy JT

bioRxiv : the preprint server for biology 20230119

Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features is poorly understood. To identify molecular pathways that contribute to synaptic diversity, single neuron PatchSeq RNA profiling was performed on <i>Drosophila</i> tonic and phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while phasic motoneurons form stronger depressing synapses onto mult ...[more]

PMID: 36711745

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Project description:IntroductionFibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables.Materials and methodsIn this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity.ResultsFifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = -0.5, p = 0.009).ConclusionOur results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.

Dataset Information

Molecular Logic of Synaptic Diversity Between Drosophila Tonic and Phasic Motoneurons.

Publications

Molecular Logic of Synaptic Diversity Between <i>Drosophila</i> Tonic and Phasic Motoneurons.

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