Dopamine maintains network synchrony via direct modulation of gap junctions in the crustacean cardiac ganglion
- University of Missouri, United States
Abstract
The Large Cell (LC) motor neurons of the crab cardiac ganglion have variable membrane conductance magnitudes even within the same individual, yet produce identical synchronized activity in the intact network. In a previous study we blocked a subset of K+ conductances across LCs, resulting in loss of synchronous activity (Lane et al., 2016). In this study, we hypothesized that this same variability of conductances makes LCs vulnerable to desynchronization during neuromodulation. We exposed the LCs to serotonin (5HT) and dopamine (DA) while recording simultaneously from multiple LCs. Both amines had distinct excitatory effects on LC output, but only 5HT caused desynchronized output. We further determined that DA rapidly increased gap junctional conductance. Co-application of both amines induced 5HT-like output, but waveforms remained synchronized. Furthermore, DA prevented desynchronization induced by the K+ channel blocker tetraethylammonium (TEA), suggesting that dopaminergic modulation of electrical coupling plays a protective role in maintaining network synchrony.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institutes of Health (R01MH046742-29)
- David J Schulz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Lane et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dopamine maintains network synchrony via direct modulation of gap junctions in the crustacean cardiac ganglion
eLife 7:e39368.
https://doi.org/10.7554/eLife.39368
Further reading
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- Evolutionary Biology
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The cerebral cortex displays a bewildering diversity of shapes and sizes across and within species. Despite this diversity, we present a universal multi-scale description of primate cortices. We show that all cortical shapes can be described as a set of nested folds of different sizes. As neighbouring folds are gradually merged, the cortices of 11 primate species follow a common scale-free morphometric trajectory, that also overlaps with over 70 other mammalian species. Our results indicate that all cerebral cortices are approximations of the same archetypal fractal shape with a fractal dimension of df = 2.5. Importantly, this new understanding enables a more precise quantification of brain morphology as a function of scale. To demonstrate the importance of this new understanding, we show a scale-dependent effect of ageing on brain morphology. We observe a more than fourfold increase in effect size (from two standard deviations to eight standard deviations) at a spatial scale of approximately 2 mm compared to standard morphological analyses. Our new understanding may, therefore, generate superior biomarkers for a range of conditions in the future.
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- Medicine
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Background:
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.
Methods:
High-resolution mass spectrometry lipidomics was applied to quantify d=255 different lipid mediators in the blood of n=31 patients drawn before and after paclitaxel therapy for breast cancer treatment. A variety of supervised statistical and machine-learning methods was applied to identify lipids that were regulated during paclitaxel therapy or differed among patients with and without post-therapeutic neuropathy.
Results:
Twenty-seven lipids were identified that carried relevant information to train machine learning algorithms to identify, in new cases, whether a blood sample was drawn before or after paclitaxel therapy with a median balanced accuracy of up to 90%. One of the top hits, sphinganine-1-phosphate (SA1P), was found to induce calcium transients in sensory neurons via the transient receptor potential vanilloid 1 (TRPV1) channel and sphingosine-1-phosphate receptors.SA1P also showed different blood concentrations between patients with and without neuropathy.
Conclusions:
Present findings suggest a role for sphinganine-1-phosphate in paclitaxel-induced biological changes associated with neuropathic side effects. The identified SA1P, through its receptors, may provide a potential drug target for co-therapy with paclitaxel to reduce one of its major and therapy-limiting side effects.
Funding:
This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG, Grants SFB1039 A09 and Z01) and by the Fraunhofer Foundation Project: Neuropathic Pain as well as the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD). This work was also supported by the Leistungszentrum Innovative Therapeutics (TheraNova) funded by the Fraunhofer Society and the Hessian Ministry of Science and Arts. Jörn Lötsch was supported by the Deutsche Forschungsgemeinschaft (DFG LO 612/16-1).
