Investigating the role of astrocytes and noradrenaline as critical regulators of neuronal circuit excitability.

Proper information processing in the mammalian brain requires tight regulation of neuronal excitability, which can be modified by so-called neuromodulators, such as noradrenaline. Noradrenaline (NA) is known to prime the healthy brain for sensory input and to facilitate memory formation. However, hyperactivity of neurons is deleterious and can lead to disease, of which the classic example is epilepsy. Crucially, NA appears to dampen down excessive neuronal excitability, exerting strong anti-convulsive effects in epilepsy. However, the molecular and cellular bases of NA activity are unclear. Neurons are only one type of cell in the brain. There is an increasing amount of information suggesting that other cell types also have critical functions in the adult brain. One of these cell types is the astrocyte and there is strong circumstantial evidence linking these cells to the activity of NA in the healthy and epileptic brain. The aim of this project, therefore, is to investigate the precise roles of astrocytes and NA in regulating the excitability of neuronal circuits. Establishing a central role for astrocytes in controlling neuromodulator-mediated regulation of excitability would represent a major finding in neuroscience, placing key aspects of brain activity under direct astrocyte control, and providing new avenues to explore for the development of next generation therapeutics.