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4 YEAR PhD IN NEUROSCIENCE

David Attwell

Neuron-glial interactions and brain energy supply

The Attwell lab studies how neurons interact with glial cells and with the vasculature, and how energy is supplied to the brain and used.

Our studies of the vasculature have identified a new locus for control of brain blood flow: capillary pericytes (Peppiatt et al., 2006; Attwell et al., 2010; Hall et al., 2014). These increase blood flow to power neurons in physiological conditions, but in ischaemia they constrict capillaries and die in rigor, increasing neuronal death. Ongoing studies are characterising how the tone of these cells is regulated, and how to prevent them constricting and dying in ischaemia. We are also investigating the properties of human pericytes in living tissue taken from neurosurgical operations, and extending our work on brain pericytes to other organs.

Our theoretical and experimental work on brain energy use has characterised how the brain minimises its energy consumption to maximise information processing (Harris et al, 2012, 2015).

We carry out experiments on the development, plasticity and pathology of myelin, and have recently characterised a novel TRP channel based mechanism by which myelin is damaged in ischaemia (Hamilton et al., 2016).

We are interested in how astrocytes interact with neurons via calcium-dependent signalling (Bazargani & Attwell, 2016).

We are intensively studying the properties of microglia (the brain’s immune cells), how they survey the brain, and how they behave in pathology.

Available projects include the following, which will typically involve brain slicing, 2-photon or confocal imaging, immunocytochemistry, patch-clamping, imaging of cell death and theoretical modelling.

(1) Studying mechanisms regulating pericyte tone and preventing pericyte death after stroke

(2) Ischaemic damage to oligodendrocytes

(3) Myelination of auditory brainstem axons

(4) Development, plasticity and pathology of the node of Ranvier

(5) The role of microglia in neuron-astrocyte signalling and Alzheimer’s disease

References

Attwell, D., Buchan, A.M., Charpak, S., Lauritzen, M., Macvicar, B.A. & Newman, E.A. (2010) Glial and neuronal control of brain blood flow. Nature 468, 232-243.

Bazargani, N. & Attwell, D. (2016) Astrocyte calcium signalling: the third wave. Nature Neuroscience 19, 182-189.

Hall, C.N., Reynell, C., Gesslein, B., Hamilton, N.B., Mishra, A., Sutherland, B., O’Farrell, F.M., Buchan, A.M., Lauritzen, M. & Attwell, D. (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508, 55-60.

Hamilton, N.B., Kolodziejczyk, K., Kougioumtzidou, E. & Attwell, D. (2016) Proton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia. Nature 529, 523-527.

Harris, J.J., Jolivet, R. & Attwell, D. (2012) Synaptic energy use and supply. Neuron 75, 762-777.

Harris, J.J., Jolivet, R., Engl, E. & Attwell, D. (2015) Energy-efficient information transfer by visual pathway synapses. Current Biology 25, 3151-3160.

Peppiatt, C., Howarth, C., Mobbs, P. & Attwell, D. (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443, 700-704.

David Attwell, Andrew Huxley Building, UCL

d.attwell@ucl.ac.uk http://www.ucl.ac.uk/npp/research/da