The role of diurnal intracellular chloride changes in cortical network activity and plasticity. (360G-Wellcome-206500_Z_17_Z)

Cyclical changes between sleeping and waking states are a fundamental feature of mammalian physiology. During these different states, our brains exhibit distinct patterns of network activity and different capacities to learn. An understanding of the cellular mechanisms that underlie these processes is important to fully appreciate how daily changes in brain function contribute in health and disease. Here I propose to explore how dynamic changes in synaptic inhibition influence the mammalian cortex across the sleep-wake cycle. This will entail experiments that span cellular and systems levels of neuroscience, and that capitalise on my experience in developing novel applications of optogenetic tools. Using the mouse as a model system, I will examine the hypothesis that diurnal changes in intracellular chloride contribute to sleep-wake associated changes in cortical brain states and synaptic plasticity. To achieve this, my key goals are as follows. (i) I will establish the cellular and systems mechanisms that regulate the diurnal variation of intracellular chloride in mouse cortex. (ii) I will examine how diurnal chloride variation affects cortical network oscillations across the sleep-wake cycle. (iii) I will investigate the physiological impact of diurnal chloride variation upon cortical synaptic plasticity, by examining learning mechanisms during the day and night.