ArticleProceedings of the National Academy of Sciences of the United States of America2022
Lactate supply overtakes glucose when neural computational and cognitive loads scale up.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Review
- Irregular and bursty neuronal firing extend spike-timing dependent plasticity window to behavioral timescales.iScience · 2026Article
- Metabolism Controls the Timing of Human Brain Development and Maturation.Journal of inherited metabolic disease · 2026Review
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Early functional changes and plasma GFAP in Swedish families with Autosomal Dominant Alzheimer's disease mutations.Translational psychiatry · 2026Article
- The Molecular Signature of Astrocyte Response to Hypoxia Outlines the Metabolic and Cell Survival Mechanisms for Neuroprotection.Neurochemical research · 2026Article
- Special characteristics of human astrocytes and their roles in brain homeostasis.Neuroscience applied · 2026Review
- Compensatory transporter upregulation facilitates retinal ganglion cell survival in glaucoma after MCT2 elimination.Frontiers in cell and developmental biology · 2026Article
- The glioma neuron symbiosis hypothesis-cellular and molecular mechanistic considerations.Frontiers in neuroscience · 2026Article
- Chronic Stress and Astrocyte Dysfunction in Depression: Molecular Mechanisms and Gene Expression Changes.Antioxidants (Basel, Switzerland) · 2025Review
- The neuron-astrocyte metabolic unit as a cornerstone of brain energy metabolism in health and disease.Nature metabolism · 2025Review
- Neuronal activity-induced GLUT3 plasma translocation supports energy demands for memory acquisition.Communications biology · 2025Article
- Intracellular lactate dynamics iniScience · 2025Article
- Astrocytes in maintaining neuronal health and brain function: interplay of aging, diet, and environment.Metabolic brain disease · 2025Review
- Exercise-Induced Hippocampal Neurogenesis Is Attenuated by Inhibition of Monocarboxylate Transporter 2.Molecular neurobiology · 2025Article
- Elucidating reaction dynamics in a model of human brain energy metabolism.PLoS computational biology · 2025Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- A neurometabolic mechanism involving dmPFC/dACC lactate in physical effort-based decision-making.Molecular psychiatry · 2025Article
- Acute Concurrent Exercise Improves Inhibitory Control Without Mediating the Role of Lactate: An Event-Related Potential Study.Sports medicine - open · 2025Article
- The Effects of Exercise on Hippocampus-Based Cognitive Dysfunction in Type 2 Diabetes Mellitus: A Possible Involvement of Hippocampal Monocarboxylate Transporter 2.Advances in neurobiology · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neural 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.
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