Global changes in patterns of neuronal activity or brain state are the first phenomenon recorded in the awake human brain (1). Changes in brain state are present in recordings of neocortical activity from mouse to man. It is now thought that changes in brain state are fundamental to normal brain function and neuronal computation. Despite their importance, we have very little idea about the underlying neuronal mechanisms that generate them or their precise impact on neuronal processing and behaviour. In previous work we have characterised brain state changes in a well characterised model for neuroscience research the mouse whisker system. We have recorded changes in the brain state in mouse cortex during whisker movements (2). In this proposal, we aim to use the mouse whisker system further to investigate the mechanisms and functions of changes in brain state. First we will use state of the art techniques to record and manipulate neuronal activity in the awake, behaving mouse to investigate the network and cellular mechanisms involved in generating brain state. Second we will use 2-photon microscopy to investigate the impact of brain state on excitatory and inhibitory synaptic integration in vivo. Finally we will use behaviourally trained mice to measure the impact of brain state changes on sensory perception and behaviour. This proposal will therefore provide fundamental insights into brain function at every step: mechanisms of changes in brain state, how neurons communicate with eachother and how the brain controls sensory perception and behaviour.References1 Berger H (1929) Archiv für Psychiatrie und Nervenkrankheiten 87:527-570.2 Poulet JFA, Petersen CC (2008) Nature 454:881-885.