Dr Catherine Hall
Controlling the brain’s energy supply in health and disease
Brain activity is energetically expensive. To fuel regional brain activity, active neurons signal to dilate local blood vessels, increasing blood flow, seemingly matching energy supply with demand. This also means that the blood oxygen-dependent (BOLD) signal measured using fMRI generally correlates with neuronal activity. BOLD-fMRI is now used widely in cognitive neuroscience as an indicator of regional neuronal activity.
Understanding how active neurons signal to blood vessels is really important for understanding how brain function is sustained as well as understanding BOLD signals: Neurovascular coupling properties vary across brain regions and stimulation conditions. Such variability raises questions as to whether the brain’s energy use is always adequately coupled with supply, and has serious implications for the interpretation of the BOLD signal, as changes in neuronal activity may not always result in a change in BOLD. In our lab we research how neurons control local blood flow, and how the balance between energy supply and demand is affected by different disease states (e.g. Alzheimer’s disease, high fat diet). We are using 2-photon imaging and optical measurement of haemodynamic responses in mouse cortex and hippocampus, to measure neuronal, microglial and vascular responses during visual stimulation or while mice navigate a virtual reality environment.
A project in our lab could investigate when, why and how neurovascular coupling properties vary and how such variations might affect brain function. A project could focus on physiological scenarios, such as how neurovascular coupling varies when different behaviours engage different brain states, or which neurons are most important for controlling local blood vessels. Alternatively a project could investigate what happens during pathological conditions where the brain’s energy supply is impaired (e.g. models of hypoperfusion or Alzheimer’s disease). To answer these questions, a combination of in vivo 2-photon imaging of neuronal activity and blood vessels in awake, behaving mice and wide-field imaging of brain slices will be used. In addition, computer modeling could be used to predict the amount of energy used and supplied from measured neuronal and vascular responses, and immunohistochemistry will detect activation of different cell populations and neurovascular signaling molecules.
- Shaw, K., Bell, L., Boyd, K., Grijseels, D.M., Clarke, D., Bonnar, O., Crombag, H.S. and Hall, C. N. (2021) Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences. Nature Communications 12 (1), 1-16
- Clarke, Devin, Crombag, Hans S and Hall, Catherine N (2021) An open-source pipeline for analysing changes in microglial morphology. Open Biology, 11 (8). 210045 1-15. ISSN 2046-2441
- Grijseels, Dori M, Shaw, Kira, Barry, Caswell and Hall, Catherine N (2021) Choice of method of place cell classification determines the population of cells identified. PLoS Computational Biology, 17 (7). a1008835 1-32. ISSN 1553-734X
- Hall , C.N., Reynell, C., Gesslein, B., Hamilton, N.B., Mishra, A., Sutherland, B.A., O’Farrell, F., Buchan, A., Lauritzen, M. and Attwell, D. (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 508(7494):55-60
- Hall, C.N., Klein-Flügge, M, Howarth, C and Attwell, D. (2012) Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing. J. Neurosci. 32, 8940-51
- Hamilton, N., Attwell, D. and Hall, C.N. (2010) Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Front. Neuroenerg. 2:5. doi:10.3389/fnene.2010.00005.
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