Brain Energy Lab Principal investigator: Dr catherine hall

Behavioural and Clinical Neuroscience Group, School of Psychology, Unversity of Sussex

NEWS! Now recruiting a technician to support work on Alzheimer's disease, brain energy and memory circuitry.

NEWS! PhD studentship available co-supervised by Catherine Hall, on dissecting neural circuits underlying contextual memory (Main supervisor Dr Hans Crombag)

NEWS! Dr Kira Shaw has joined the lab, to establish 2-photon imaging of neurovascular coupling in the hippocampus of awake, behaving mice (funded by an MRC Discovery Award).

NEWS! The Brain Energy Lab will study brain oxygenation changes during the onset of Alzheimer's disease: PhD student Orla Bonnar has joined the lab, as part of the Alzheimer's Society Doctoral Training Centre. This work is also funded by a recent Academy of Medical Sciences/Wellcome Trust Springboard award.

We want to understand how the brain balances its energy supply with demand - and how variations in this balance affect brain function. Specifically, we want to learn which vascular cells control the brain's energy supply, and how much neurovascular coupling between energy supply (blood flow) and demand (neuronal activity) varies during normal and pathological brain function. For example, we are investigating whether neurovascular function changes during different arousal states, or in conditions such as Alzheimer’s disease and obesity. To do this, we image blood vessels in brain slices and in vivo, in behaving mice, while manipulating neuronal activity pharmacologically or using physiological stimuli, and imaging neuronal activity using genetically encoded calcium indicators. By concurrently measuring neuronal activity and vascular responses during different conditions, we will be able to determine which factors modulate the neurovascular coupling relationship. Our results will be important for understanding how brain activity is fuelled and how the brain’s energy supply is affected by disease. Because human functional magnetic resonance imaging (fMRI) measures blood flow as a surrogate of neuronal activity, our results will also be important for understanding what fMRI signals actually tell us about neuronal activity.

In our lab, we use several imaging techniques to probe neurovascular function. Clockwise from left: 1) Investigating inflammation and the vasculature: Confocal image of a live hippocampal brain slice, with blood vessels and microglia labelled with IB4 (cyan) and astrocytes labelled with SR101 (red). 2) Probing neurovascular coupling in vivo: 2-photon image of a visual cortex capillary (red) and VIP interneuron presynaptic terminals in a behaving mouse (data collected by CH, Rozan Vroman and Leon Lagnado). 3) Head of lab: Dr Catherine Hall 4) Investigating vascular mural cell anatomy: Confocal image of a fixed slice of cortex from mice expressing the fluorescent protein DsRed in vascular mural cells.
Brain capillaries can be imaged in behaving mice, by intravenously injecting a fluorescent dye and imaging the brain with a 2-photon microscope. Either the whole capillary can be imaged (A), so changes in area can be measured, or a line can be scanned very fast (C), allowing blood cell velocity to be determined. When mice run on a ball, capillaries in somatosensory cortex dilate (B), and blood cells move faster (D). Data collected by CH in collaboration with Patrick Drew, at Pennsylvania State University.


Devin Clarke - PhD student

Imaging the brain's capillary network

We can fill the brain's blood vessels with a fluorescent gel (green) and label different sorts of brain cells. Here the basement membrane of blood vessels and microglia are labelled with IB4 (red). From these images, we can see how blood vessels and inflammatory cells such as microglia are affected by drugs, diets or diseases that can affect brain function.

Do monoamines affect neurovascular coupling?

Katie Boyd, PhD student

My project will test whether transmitters such as noradrenaline and dopamine alter the relationship between neuronal activity and vascular responses. To explore this, I image blood vessels in brain slices, and apply drugs to change blood vessel diameters. I also measure neuronal and blood vessel responses in vivo, in conditions where monoamine release varies.

In this image, a capillary is constricting in response to applied noradrenaline and dilating in response to glutamate.

How does vascular function change across the vascular bed?

Matt Hammond-Haley, Brighton and Sussex Medical School Individual Research Project Student

I use confocal imaging of fluorescently labelled tissue to study how vascular function changes across cardiac and cerebral vascular beds, and how vascular function is affected by drugs such as cocaine.

Here, the heart capillary bed has been filled with a green gel, and pericytes expressing NG2 have been labelled immunohistochemically in red. DAPI-stained nuclei are shown in blue.

Data collected in collaboration with Dr Hans Crombag

Example publications:

Hall, C.N., Howarth, C, Kurth-Nelson, Z and Mishra, A. (2016) Interpreting BOLD: towards a dialogue between cellular and cognitive neuroscience. Philosophical Transactions of the Royal Society B, 371(1705). pii: 20150348. doi: 10.1098/rstb.2015.0348.

Attwell, D, Mishra, A, Hall, C.N., O’Farrell, F., Dalkara, T. (2015) What is a pericyte? J Cereb Blood Flow Metab October 14, 2015 0271678X15610340

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



Our work is currently supported by the Academy of Medical Sciences and the Wellcome Trust, through a Springboard Award to Catherine Hall, as well as the Physiological Society, the Alzheimer's Society, the MRC via an MRC Discovery Award, and the University of Sussex. We have also had recent support from the Royal Society.

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Catherine Hall

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