Abstract
SummaryLactate 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.
Highlights
Lactate is a three-carbon, electron-rich metabolite that can be produced and released by various cell types of the body (Brooks, 2018)
We show that sole lactate disturbs electrical gamma and theta-gamma oscillations in hippocampal networks by either attenuation or neural bursts
Lactate is linked to oxidative ATP synthesis in mitochondria, which requires conversion back to pyruvate through the redox enzyme lactate dehydrogenase (LDH), the tricarboxylic acid cycle, and molecular oxygen serving as the final electron acceptor at the respiratory chain (Brooks, 2018; Dienel, 2019)
Summary
Lactate is a three-carbon, electron-rich metabolite that can be produced and released by various cell types of the body (Brooks, 2018). Lactate is linked to oxidative ATP synthesis in mitochondria, which requires conversion back to pyruvate through the redox enzyme lactate dehydrogenase (LDH), the tricarboxylic acid cycle, and molecular oxygen serving as the final electron acceptor at the respiratory chain (Brooks, 2018; Dienel, 2019). Lactate can be released from glial cells, such as astrocytes and oligodendrocytes (Pellerin and Magistretti, 1994; Gandhi et al, 2009; Saab et al, 2016), and it can enter the brain parenchyma from the blood when physical activity increases plasma lactate to as high as 20 mM (Rasmussen et al, 2010; Dienel, 2019). The shuttling of lactate between brain cells depends on various monocarboxylic acid transporters (MCTs) and follows the local concentration gradient (Barros, 2013; Machler et al, 2016)
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