The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms

Carlos Bas-Orth, Justin Schneider, Andrea Lewen, Jamie McQueen, Kerstin Hasenpusch-Theil, Thomas Theil, Giles E. Hardingham, Hilmar Bading, Oliver Kann

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The role of the mitochondrial calcium uniporter (MCU) gene (Mcu) in cellular energy homeostasis and generation of electrical brain rhythms is widely unknown. We investigated this issue in mice and rats using Mcu-knockout and -knockdown strategies in vivo and in situ and determined the effects of these genetic manipulations on hippocampal gamma oscillations (30–70 Hz) and sharp wave-ripples. These physiological network states require precise neurotransmission between pyramidal cells and inhibitory interneurons, support spike-timing and synaptic plasticity and are associated with perception, attention and memory. Absence of the MCU resulted in (i) gamma oscillations with decreased power (by >40%) and lower synchrony, including less precise neural action potential generation (‘spiking'), (ii) sharp waves with decreased incidence (by about 22%) and decreased fast ripple frequency (by about 3%) and (iii) lack of activity-dependent pyruvate dehydrogenase dephosphorylation. However, compensatory adaptation in gene expression related to mitochondrial function and glucose metabolism was not detected. These data suggest that the neuronal MCU is crucial for the generation of network rhythms, most likely by influences on oxidative phosphorylation and perhaps by controlling cytoplasmic Ca2+ homeostasis. This work contributes to an increased understanding of mitochondrial Ca2+ uptake in cortical information processing underlying cognition and behaviour.
Original languageEnglish
Pages (from-to)2225-2239
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number11
Early online date13 Nov 2019
Publication statusPublished - 1 Nov 2020


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