Physiological synaptic activity and recognition memory require astroglial glutamine

Giselle Cheung (1) , Danijela Bataveljic (1) , Josien Visser (1, 2) , Naresh Kumar (3) , Julien Moulard (1, 2) , Glenn Dallérac (4) , Daria Mozheiko (1, 2) , Astrid Rollenhagen (5) , Pascal Ezan (1) , Cédric Mongin (3) , Oana Chever (1, 6) , Alexis-Pierre Bemelmans (7) , Joachim Lübke (8) , Isabelle Leray (3) , Nathalie Rouach (1)

1 CIRB - Centre interdisciplinaire de recherche en biologie
2 ED 158 - 3C - Ecole doctorale Cerveau Cognition et Comportement [Paris]
3 PPSM - Photophysique et Photochimie Supramoléculaires et Macromoléculaires
4 NeuroPSI - Institut des Neurosciences Paris-Saclay
5 INM-1 - Institute of Neuroscience and Medicine [Jülich]
6 DC2N - Différenciation et communication neuronale et neuroendocrine
7 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
8 Department of Psychiatry, Psychotherapy and Psychosomatics [Aachen]

Abstract 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.

Domains: Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Neurobiology; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Psychology and behavior; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Cognitive Sciences

Giselle Cheung, Danijela Bataveljic, Josien Visser, Naresh Kumar, Julien Moulard, et al.. Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications, 2022, 13 (1), pp.753. ⟨10.1038/s41467-022-28331-7⟩. ⟨hal-03625240⟩