Inhibiting Glutamate Activity during Consolidation Suppresses Age-Related Long-Term Memory Impairment in Drosophila
Autor: | Minoru Saitoe, Kyoko Ofusa, Junjiro Horiuchi, Tomoko Masuda, Motomi Matsuno |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
animal structures Mutant 02 engineering and technology Article Behavioral Neuroscience 03 medical and health sciences Gene expression lcsh:Science Transcription factor Multidisciplinary Model Organism Consolidation (soil) Cell adhesion molecule Chemistry Long-term memory fungi Glutamate receptor 021001 nanoscience & nanotechnology Cell biology 030104 developmental biology nervous system lcsh:Q Memory consolidation Molecular Neuroscience 0210 nano-technology psychological phenomena and processes |
Zdroj: | iScience iScience, Vol 15, Iss, Pp 55-65 (2019) |
ISSN: | 2589-0042 |
Popis: | Summary In Drosophila, long-term memory (LTM) formation requires increases in glial gene expression. Klingon (Klg), a cell adhesion molecule expressed in both neurons and glia, induces expression of the glial transcription factor, Repo. However, glial signaling downstream of Repo has been unclear. Here we demonstrate that Repo increases expression of the glutamate transporter, EAAT1, and EAAT1 is required during consolidation of LTM. The expressions of Klg, Repo, and EAAT1 decrease upon aging, suggesting that age-related impairments in LTM are caused by dysfunction of the Klg-Repo-EAAT1 pathway. Supporting this idea, overexpression of Repo or EAAT1 rescues age-associated impairments in LTM. Pharmacological inhibition of glutamate activity during consolidation improves LTM in klg mutants and aged flies. Altogether, our results indicate that LTM formation requires glial-dependent inhibition of glutamate signaling during memory consolidation, and aging disrupts this process by inhibiting the Klg-Repo-EAAT1 pathway. Graphical Abstract Highlights • Expression of the Eaat1 glutamate transporter increases during memory consolidation • This suggests that memory consolidation requires reduced glutamate signaling • Aged flies have reduced long-term memory and reduced Eaat1 induction • Increasing Eaat1 or inhibiting glutamate activity improves memory in aged flies Behavioral Neuroscience; Molecular Neuroscience; Model Organism |
Databáze: | OpenAIRE |
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