Magnesium efflux from Drosophila Kenyon cells is critical for normal and diet-enhanced long-term memory.

Yanying Wu,Kristijan D Jovanoski,Hiroaki Miki,Scott Waddell,Eleonora Meschi,Yosuke Funato

doi:10.7554/elife.61339

Yanying Wu, Kristijan D Jovanoski + Show 4 more

Open Access

https://doi.org/10.7554/elife.61339

Copy DOI

Journal: eLife	Publication Date: Nov 26, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: University of Oxford, Osaka University

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 (KCs) 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 KC Mg2+. We propose that regulated neuronal Mg2+ efflux is critical for normal and Mg2+-enhanced memory.

Highlights

Magnesium (Mg2+) plays a critical role in cellular metabolism and is considered to be an essential cofactor for more than 350 enzymes (Romani and Scarpa, 2000; Vink and Nechifor, 2011)
Wild-type flies fed for 4 days before training with food supplemented with additional magnesium chloride (MgCl2) exhibited significantly enhanced 24 hr memory performance
Flies expressing Nmdar1RNAi in neurons retained robust Mg2+-enhanced memory ab (Figure 1—figure supplement 1C). These results suggest that Mg2+-enhanced memory does not alter expression of glutamate receptors, or require N-methyl-D-aspartate glutamate receptor (NMDAR) function in ab Kenyon cells (KCs)

Summary

Introduction

Magnesium (Mg2+) plays a critical role in cellular metabolism and is considered to be an essential cofactor for more than 350 enzymes (Romani and Scarpa, 2000; Vink and Nechifor, 2011). Perhaps surprisingly, increasing brain Mg2+ through diet can enhance neuronal plasticity and memory performance of young and aged rodents, measured in a variety of behavioral tasks (Slutsky et al, 2010; Landfield and Morgan, 1984; Mickley et al, 2013; Abumaria et al, 2013). Elevated Mg2+ reduced cognitive deficits in a mouse model of Alzheimer’s disease (Li et al, 2013) and enhanced the extinction of fear memories (Abumaria et al, 2011). These apparently beneficial effects have led to the proposal that dietary Mg2+ may have therapeutic value for patients with a variety of memory-related problems (Billard, 2011).

Methods

Results

Conclusion