Lactate supply overtakes glucose when neural computational and cognitive loads scale up
Magistretti, Pierre J.
KAUST DepartmentBioscience Program
KAUST Smart Health Initiative
Biological and Environmental Science and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/677940
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AbstractNeural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram is unclear. To solve this question, we asked whether neuronal fueling by glucose or lactate scales differently upon increasing neural computation and cognitive loads. Here, using electrophysiology, two-photon imaging, cognitive tasks, and mathematical modeling, we show that both glucose and lactate are involved in engram formation, with lactate supporting long-term synaptic plasticity evoked by high-stimulation load activity patterns and high attentional load in cognitive tasks and glucose being sufficient for less demanding neural computation and learning tasks. Indeed, we show that lactate is mandatory for demanding neural computation, such as theta-burst stimulation, while glucose is sufficient for lighter forms of activity-dependent long-term potentiation (LTP), such as spike timing–dependent plasticity (STDP). We find that subtle variations of spike number or frequency in STDP are sufficient to shift the on-demand fueling from glucose to lactate. Finally, we demonstrate that lactate is necessary for a cognitive task requiring high attentional load, such as the object-in-place task, and for the corresponding in vivo hippocampal LTP expression but is not needed for a less demanding task, such as a simple novel object recognition. Overall, these results demonstrate that glucose and lactate metabolism are differentially engaged in neuronal fueling depending on the complexity of the activity-dependent plasticity and behavior.
CitationDembitskaya, Y., Piette, C., Perez, S., Berry, H., Magistretti, P. J., & Venance, L. (2022). Lactate supply overtakes glucose when neural computational and cognitive loads scale up. Proceedings of the National Academy of Sciences, 119(47). https://doi.org/10.1073/pnas.2212004119
SponsorsWe thank the members of the L.V. laboratory for helpful suggestions and critical comments. We thank Giuseppe Gangarossa and Marika Nosten-Bertrand for their helpful suggestions for behavioral tasks, Marie Vandecasteele for technical and analysis assistance for preliminary in vivo electrophysiological recordings, and Ilya Prokin for the custom-made software for calcium transient analysis. This work was supported by Collège de France, Inserm, CNRS and Fondation Bettencourt Schueller.
Except where otherwise noted, this item's license is described as Archived with thanks to Proceedings of the National Academy of Sciences under a Creative Commons license, details at: https://creativecommons.org/licenses/by/4.0/
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