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

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.