Baseline oxygen consumption decreases with cortical depth

Abstract

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase—the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than reflecting baseline energy needs. Our study provides to our knowledge the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards better understanding of brain energy metabolism.

Lactate as a supplemental fuel for synaptic transmission and neuronal network oscillations: Potentials and limitations

“…During spontaneous asynchronous neuronal network activity, for example, the pO 2 was around 140 and 50 mmHg at the slice surface and the core (about 165 μm depth), respectively, when slices cultures were maintained at the interface between ACSF and a gas mixture containing 20% O 2 and 5% CO 2 (‘interface recording condition’) (Huchzermeyer et al, 2013). Such levels of pO 2 in the slice core are close to those determined under normoxic conditions in the rodent brain (Liu et al, 1995; Mächler et al, 2022; Roche et al, 2019; Vovenko, 1999).…”

“…The CMRO2 was somewhat lower (3.0 mM/min) in acute rat hippocampal slices (Hollnagel et al, 2020). For the cortex of mouse and rat, the estimates of CMRO2 range between 1.9 and 2.7 mM/min, depending on the cortical depth and the anesthesia level (Enager et al, 2009; Gagnon et al, 2015; Mächler et al, 2022; Zhu et al, 2007). The high CMRO2 obtained during gamma oscillations (Hollnagel et al, 2020; Huchzermeyer et al, 2013; Schneider et al, 2019) might reflect the significant reduction of network activity and energetics of about half during anesthesia in vivo (Aksenov et al, 2015; Lyons et al, 2016; Shulman et al, 2009; Xu et al, 2022), the persistent nature of the gamma oscillations ex vivo, and the high spatial resolution of oxygen recordings ex vivo (Schneider et al, 2019).…”

Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer’s disease

“…Recent advances in optical coherence tomography (OCT) will help delineate the precise trajectory of hemodynamic alterations during AD by enabling near-lifespan tracking of microvascular morphology and function (107). Lastly, estimating cerebral metabolic of oxygen (CMRO2) in response to inflammation using Krogh-Erlang model (108) or the recent proposed ODACITI model (109) could further validate our findings of increased oxygen extraction in inflamed AD brain tissue.…”

Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCO2, and pO2

“…Another limitation of this study is that the calculations of average tissue and , do not provide information on their microscopic blood and tissue distribution within a neurovascular unit. Based upon recent studies using high resolution optical imaging, regional levels within a neurovascular unit vary between approximately 2.0–0.5 times the mean value (Gould et al, 2017; Li et al, 2019; Lyons et al, 2016; Mächler et al, 2022; Moeini et al, 2018, 2019, 2020), The lower end of this range may explain the sensitivity of brain function to decreases in being greater than anticipated from average values. Due to its 20‐fold higher diffusivity, the range of is anticipated to be similar to the difference in arteriole and venule values (see Equation 34).…”