Mitochondrial Functional State Impacts Spontaneous Neocortical Activity and Resting State fMRI

Basavaraju G. Sanganahalli, Peter Herman, Fahmeed Hyder, Sridhar S. Kannurpatti

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Mitochondrial Ca2+ uptake, central to neural metabolism and function, is diminished in aging whereas enhanced after acute/sub-acute traumatic brain injury. To develop relevant translational models for these neuropathologies, we determined the impact of perturbed mitochondrial Ca2+ uptake capacities on intrinsic brain activity using clinically relevant markers. From a multi-compartment estimate of probable baseline Ca2+ ranges in the brain, we hypothesized that reduced or enhanced mitochondrial Ca2+ uptake capacity would decrease or increase spontaneous neuronal activity respectively. As resting state fMRI-BOLD fluctuations and stimulus-evoked BOLD responses have similar physiological origins [1] and stimulus-evoked neuronal and hemodynamic responses are modulated by mitochondrial Ca2+ uptake capacity [2,3] respectively, we tested our hypothesis by measuring hemodynamic fluctuations and spontaneous neuronal activities during normal and altered mitochondrial functional states. Mitochondrial Ca2+ uptake capacity was perturbed by pharmacologically inhibiting or enhancing the mitochondrial Ca2+ uniporter (mCU) activity. Neuronal electrical activity and cerebral blood flow (CBF) fluctuations were measured simultaneously and integrated with fMRI-BOLD fluctuations at 11.7T. mCU inhibition reduced spontaneous neuronal activity and the resting state functional connectivity (RSFC), whereas mCU enhancement increased spontaneous neuronal activity but reduced RSFC. We conclude that increased or decreased mitochondrial Ca2+ uptake capacities lead to diminished resting state modes of brain functional connectivity.

Original languageEnglish (US)
Article numbere63317
JournalPloS one
Volume8
Issue number5
DOIs
StatePublished - May 1 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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