Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity

eLife

Thierry Gallopin¹  Hélène Geoffroy¹  Susumu Seino²  Hiromi Imamura³  Jochen F Staiger⁴  Jochen Roeper⁵  Richard Egger⁵  Alexandre Lacroix⁶  Benjamin Le Gac⁶  Juliette Piquet⁶  Anastassios Karagiannis⁶  Bruno Cauli⁶  Dongdong Li⁶  Régine Hepp⁶  Fabrice Plaisier⁶  Bertrand Lambolez⁶  Jérémie Naudé⁶  Jean Rossier⁷ 

[1] Brain Plasticity Unit, CNRS UMR 8249, CNRS, ESPCI Paris, Paris, France;Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan;Graduate School of Biostudies, Kyoto University, Kyoto, Japan;Institute for Neuroanatomy, University Medical Center Göttingen, Georg-August- University Göttingen, Goettingen, Germany;Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany;Sorbonne Université, CNRS, INSERM, Neurosciences Paris Seine - Institut de Biologie Paris Seine (NPS-IBPS), Paris, France;Sorbonne Université, CNRS, INSERM, Neurosciences Paris Seine - Institut de Biologie Paris Seine (NPS-IBPS), Paris, France;Brain Plasticity Unit, CNRS UMR 8249, CNRS, ESPCI Paris, Paris, France;

关键词: brain metabolism;    katp channel;    neocortex;    pyramidal cell;    interneuron;    Mouse;    Rat;   

DOI  :  10.7554/eLife.71424

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with KCNJ11 and ABCC8 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.

【 授权许可】

CC BY