4.8 Article

Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41467-021-23508-y

Keywords

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Funding

  1. MRC [MR/S026495/1]
  2. Royal Society [RGS/R1/191203]
  3. MRC Discovery Award [MC_PC_15071]
  4. Academy of Medical Sciences/Wellcome Trust Springboard Award
  5. Sussex Neuroscience
  6. Sussex University Research Development
  7. University of Sussex, School of Psychology
  8. Alzheimer's Society
  9. MRC [MR/S026495/1] Funding Source: UKRI

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This study compared neurovascular function in awake mice between the hippocampus and cortex, revealing decreased blood flow, blood oxygenation, and neurovascular coupling in the hippocampus due to differences in vascular network and microvascular cell function.
The hippocampus is essential for spatial and episodic memory but is damaged early in Alzheimer's disease and is very sensitive to hypoxia. Understanding how it regulates its oxygen supply is therefore key for designing interventions to preserve its function. However, studies of neurovascular function in the hippocampus in vivo have been limited by its relative inaccessibility. Here we compared hippocampal and visual cortical neurovascular function in awake mice, using two photon imaging of individual neurons and vessels and measures of regional blood flow and haemoglobin oxygenation. We show that blood flow, blood oxygenation and neurovascular coupling were decreased in the hippocampus compared to neocortex, because of differences in both the vascular network and pericyte and endothelial cell function. Modelling oxygen diffusion indicates that these features of the hippocampal vasculature may restrict oxygen availability and could explain its sensitivity to damage during neurological conditions, including Alzheimer's disease, where the brain's energy supply is decreased. The hippocampus is particularly sensitive to hypoxia but it has been difficult to study blood flow in this region. Here the authors compare the neurovascular function of the hippocampus and cortex and in awake mice, and find differences associated with microvascular structure.

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