Magnesium efflux from Drosophila Kenyon Cells is critical for normal and diet-enhanced long-term memory
- University of Oxford, United Kingdom
- Osaka University, Japan
Abstract
Dietary magnesium (Mg2+) supplementation can enhance memory in young and aged rats. Memory-enhancing capacity was largely ascribed to increases in hippocampal synaptic density and elevated expression of the NR2B subunit of the NMDA-type glutamate receptor. Here we show that Mg2+ feeding also enhances long-term memory in Drosophila. Normal and Mg2+ enhanced fly memory appears independent of NMDA receptors in the mushroom body and instead requires expression of a conserved CNNM-type Mg2+-efflux transporter encoded by the unextended (uex) gene. UEX contains a putative cyclic nucleotide-binding homology domain and its mutation separates a vital role for uex from a function in memory. Moreover, UEX localization in mushroom body Kenyon Cells is altered in memory defective flies harboring mutations in cAMP-related genes. Functional imaging suggests that UEX-dependent efflux is required for slow rhythmic maintenance of Kenyon Cell Mg2+. We propose that regulated neuronal Mg2+ efflux is critical for normal and Mg2+ enhanced memory.
Data availability
Behaviour data from T-maza assays deposited in Dryad Digital Repository (doi:10.5061/dryad.q2bvq83hs). All other data generated or analysed during this study are included in the manuscript and supporting files.
-
Behavior data from T-maze assayDryad Digital Repository, doi:10.5061/dryad.q2bvq83hs.
-
Imaging data from ex-vivo MagIC assay Part IIDryad Digital Repository, doi:10.5061/dryad.zpc866t7d.
-
MagFRET signal from fixed brainDryad Digital Repository, doi:10.5061/dryad.dv41ns1wp.
-
Imaging data from ex-vivo MagIC assay Part IDryad Digital Repository, doi:10.5061/dryad.k0p2ngf6z.
-
Immuno-Fluorescence data from confocal scanningDryad Digital Repository, doi:10.5061/dryad.80gb5mkpx.
Article and author information
Author details
Funding
Wellcome (200846/Z/16/Z)
- Scott Waddell
European Commission (789274)
- Scott Waddell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
Version history
- Received: July 22, 2020
- Accepted: November 25, 2020
- Accepted Manuscript published: November 26, 2020 (version 1)
- Version of Record published: January 28, 2021 (version 2)
Copyright
© 2020, Wu 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.
Metrics
-
- 3,505
- views
-
- 445
- downloads
-
- 7
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Magnesium efflux from Drosophila Kenyon Cells is critical for normal and diet-enhanced long-term memory
eLife 9:e61339.
https://doi.org/10.7554/eLife.61339
Further reading
-
Magnesium supplements help boost long-term memory in flies
-
- Neuroscience
Most nervous systems combine both transmitter-mediated and direct cell-cell communication, known as 'chemical' and 'electrical' synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a 'gap junction' (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact unequivocally defines the anatomical limits of a synapse. Expansion microscopy of these single contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact's surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area functions as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of adherens junctions. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.
