The brain is disproportionately aerobic for its size, consuming 20% of inspired oxygen primarily to produce ATP via oxidative phosphorylation (1,2). However, this high oxygen demand leads to a vulnerability to hypoxia when oxygen supply drops below demand (3). 
The structure of the hippocampal vascular network, alongside pericyte and endothelial function, results in reduced blood flow and neurovascular coupling compared to the neocortex, potentially underlying the particular vulnerability of this region to hypoxia (4). Hypoxia may occur in Alzheimer’s disease (AD) development, as perturbed blood flow is observed prior to symptomatic AD (5) and a decline in hippocampal function is an early AD cognitive marker (6,7). To better understand the impact of mild hypoxia on hippocampal function we investigated how neuronal function and oxygen use was altered by a mild reduction in oxygen supply in mice in vivo and in mouse hippocampal brain slices. 
Using haemoglobin spectrometry and laser doppler flowmetry to measure changes in blood oxygen saturation and blood flow, and 2-photon microscopy to measure neuronal calcium signals in Thy1/GCaMP6f mice, our preliminary data shows that mild acute hypoxia is associated with both increased oxygen consumption and frequency of calcium events. 
We then tested whether we could recapitulate these findings in mouse hippocampal slices to provide a better model for studying underlying mechanisms.
Using a Unisense A/S oxygen microsensor, we measured depth profiles of [O2] through the pyramidal layer of the hippocampus of acute sagittal forebrain slices (300µm thickness, 32 slices from 7 mice (5 C57BLJ/6 2 Thy1xDsRed, 3 males, 4 females)), while varying bath [O2] gassing between 95% and 20%. Slice [O2] was largely hyperoxic at 95% O2, 5% CO2, approached normoxia at 58% O2, 5% CO2 and became hypoxic at 20% O2, 5% CO2, though surface [O2] in this condition was in the normoxic range (4,9). 
We then compared these profiles to theoretical [O2] profiles generated by an oxygen diffusion and Michaelis-Menten consumption model, adapted from our previous work (10) . The kinetic parameters that best fit experimental data varied depending on bath [O2] (Median: 95%:Km: 1e-5mM, Vmax:  1.2mM/min; 58%:Km: 0.0025mM, Vmax: 4mM/min; 20%:Km: 7.5e-4mM, Vmax: 0.55mM/min), predicting highly variable rates of oxygen consumption. 
Our data suggest a deviation in the O2-dependence of oxidative phosphorylation (which accounts for the bulk of oxygen consumption in the brain (1)) from simple Michaelis-Menten kinetics, which could contribute to increased oxygen consumption rates in hypoxic brain tissue . Previous work on isolated mitochondria and cytochrome c oxidase suggest that alterations in pH and cellular energy balance, such as likely occur during hypoxia, can cause such kinetic changes (11) . 
Here we show that in vivo [O2] can be recapitulated in acute mouse brain slices, and that modelled oxygen consumption kinetics are altered as bath [O2] is changed. 
In summary, our data show a counter-productive increase in hippocampal neuronal activity and oxygen use in mild hypoxia in vivo and altered O2 consumption kinetics across different [O2] in brain slices. Improving understanding of hypoxia as a potential early AD mechanism will help enable clinical translation.