Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a fluorescent probe that tracks glutamine in live cells, which provides direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.
We thank D. Mazaud and. J. Cazères for technical assistance. This work was supported by grants from the European Research Council (Consolidator grant #683154) and European Union’s Horizon 2020 research and innovation program (Marie Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD) to N.R. and from FP7-PEOPLE Marie Curie Intra-European Fellowship for career development (grant #622289) to G.C.
Cheung GT, Bataveljic D, Visser J, et al. Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. 2022;13. doi:10.1038/s41467-022-28331-7
Cheung, G. T., Bataveljic, D., Visser, J., Kumar, N., Moulard, J., Dallérac, G., … Rouach, N. (2022). Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28331-7
Cheung, Giselle T, Danijela Bataveljic, Josien Visser, Naresh Kumar, Julien Moulard, Glenn Dallérac, Daria Mozheiko, et al. “Physiological Synaptic Activity and Recognition Memory Require Astroglial Glutamine.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28331-7.
G. T. Cheung et al., “Physiological synaptic activity and recognition memory require astroglial glutamine,” Nature Communications, vol. 13. Springer Nature, 2022.
Cheung GT, Bataveljic D, Visser J, Kumar N, Moulard J, Dallérac G, Mozheiko D, Rollenhagen A, Ezan P, Mongin C, Chever O, Bemelmans AP, Lübke J, Leray I, Rouach N. 2022. Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. 13, 753.
Cheung, Giselle T., et al. “Physiological Synaptic Activity and Recognition Memory Require Astroglial Glutamine.” Nature Communications, vol. 13, 753, Springer Nature, 2022, doi:10.1038/s41467-022-28331-7.
All files available under the following license(s):
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0):