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

Nat Commun. 2021 May 27;12(1):3190. doi: 10.1038/s41467-021-23508-y.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Alzheimer Disease / physiopathology
  • Animals
  • Cell Hypoxia / physiology
  • Dementia, Vascular / physiopathology
  • Female
  • Hippocampus / blood supply*
  • Hippocampus / cytology
  • Hippocampus / diagnostic imaging
  • Hippocampus / physiopathology
  • Humans
  • Intravital Microscopy
  • Laser-Doppler Flowmetry
  • Male
  • Mice
  • Microcirculation / physiology*
  • Microscopy, Fluorescence, Multiphoton
  • Microvessels / diagnostic imaging
  • Microvessels / physiology
  • Models, Animal
  • Neocortex / blood supply*
  • Neocortex / cytology
  • Neocortex / diagnostic imaging
  • Neocortex / physiopathology
  • Neurons / metabolism
  • Neurovascular Coupling / physiology
  • Oxidative Phosphorylation
  • Oxygen / analysis
  • Oxygen / metabolism
  • Spatial Memory / physiology
  • Visual Cortex / blood supply*
  • Visual Cortex / cytology
  • Visual Cortex / physiopathology

Substances

  • Adenosine Triphosphate
  • Oxygen