Year: 2026
Type: preprint
Abstract: Dietary magnesium (Mg 2+ ) supplement enhances memory in mammals and Drosophila , but whether and how Mg 2+ changes molecular states of neurons, remains unknown. Here we used single-cell RNA sequencing to map cell-type specific transcriptional responses to memory-enhancing dietary Mg 2+ . These analyses revealed changes in Hippo-pathway gene expression in memory-relevant αβ Kenyon Cells (KCs) of the mushroom bodies. Targeted knock-down of Merlin , hippo ( hpo ) and warts demonstrated requirement in αβ KCs for Mg 2+ -enhanced, but not baseline memory. Further study of Hippo signaling identified Yorkie ( yki ) transcriptional coactivator and DNA-binding partner Scalloped ( sd ) to be required for baseline and Mg 2+ -enhanced memory. Moreover, releasing Yki::Sd of inhibition from Tondu-domain containing growth inhibitor ( Tgi ) specifically in αβ KCs enhanced memory, independent of diet. Analyses of Yki::Sd target genes identified several required in αβ KCs for baseline memory, including crb and Glut1 which are also Mg 2+ -induced in a Hippo-dependent manner in αβ KCs. These genes suggest that aiding the metabolic demands of long-term memory and facilitating structural neuronal plasticity are key mediators of Mg 2+ -induced memory enhancement. We propose pharmacological enhancement of Sd-dependent transcription, and activity of particular Sd-target genes may have therapeutic potential for memory disorders.
Institution: University of Oxford
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221173469