Lactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure

• Published in: iScience 2020-07, Vol.23 (7), p.101316-101316, Article 101316
• Main Authors: Hollnagel, Jan-Oliver, Cesetti, Tiziana, Schneider, Justus, Vazetdinova, Alina, Valiullina-Rakhmatullina, Fliza, Lewen, Andrea, Rozov, Andrei, Kann, Oliver
• Format: Article
• Language: English
• Subjects: Biochemistry; Cell Biology; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101316

Lactate shuttled from blood, astrocytes, and/or oligodendrocytes may serve as the major glucose alternative in brain energy metabolism. However, its effectiveness in fueling neuronal information processing underlying complex cortex functions like perception and memory is unclear. We show that sole lactate disturbs electrical gamma and theta-gamma oscillations in hippocampal networks by either attenuation or neural bursts. Bursting is suppressed by elevating the glucose fraction in substrate supply. By contrast, lactate does not affect electrical sharp wave-ripple activity featuring lower energy use. Lactate increases the oxygen consumption during the network states, reflecting enhanced oxidative ATP synthesis in mitochondria. Finally, lactate attenuates synaptic transmission in excitatory pyramidal cells and fast-spiking, inhibitory interneurons by reduced neurotransmitter release from presynaptic terminals, whereas action potential generation in the axon is regular. In conclusion, sole lactate is less effective and potentially harmful during gamma-band rhythms by omitting obligatory ATP delivery through fast glycolysis at the synapse. [Display omitted] •Lactate fuels network oscillations featuring low energy expenditure•Lactate can disturb the neuronal excitation-inhibition balance•Lactate attenuates neurotransmission at glutamatergic and GABAergic synapses•Lactate increases oxygen consumption, whereas neural activity can even decrease Biochemistry; Neuroscience; Cell Biology