Lactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure
Jan-Oliver Hollnagel,
Tiziana Cesetti,
Justus Schneider,
Alina Vazetdinova,
Fliza Valiullina-Rakhmatullina,
Andrea Lewen,
Andrei Rozov,
Oliver Kann
Affiliations
Jan-Oliver Hollnagel
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany
Tiziana Cesetti
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany
Justus Schneider
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany
Alina Vazetdinova
OpenLab of Neurobiology, Kazan Federal University, 420008 Kazan, Russia
Fliza Valiullina-Rakhmatullina
OpenLab of Neurobiology, Kazan Federal University, 420008 Kazan, Russia
Andrea Lewen
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany
Andrei Rozov
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany; OpenLab of Neurobiology, Kazan Federal University, 420008 Kazan, Russia
Oliver Kann
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany; Interdisciplinary Center for Neurosciences, University of Heidelberg, 69120 Heidelberg, Germany; Corresponding author
Summary: 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.
