Circuit mechanisms of cognitive control

In order to survive, an animal's behaviour must be flexible. This flexibility allows animals to react differently to the same stimuli depending on the context. How the brain selects different actions in response to the same stimulus remains a mystery. Here I propose to understand the neural mechanisms of behavioural flexibility in mice. Specifically, I will study the prefrontal cortex (PFC), given its crucial role in generating flexible cognitive behaviour in rodents, primates and humans. I have developed a novel attentional switching paradigm, wherein head-fixed mice switch between responding to and ignoring the same visual stimuli, and have combined this behaviour with 2-photon imaging and optogenetic manipulation of neurons from identified cell classes in visual cortex. Here I hypothesise that PFC cells projecting to sensory and motor areas bias the processing in these target areas in a context dependent manner, enabled through transiently reduced inhibition from specific interneurons. I will thus address the following specific aims. 1) Identify the neural population dynamics in PFC associated with attentional switching, 2) Determine the interneuron classes involved in the reorganisation of neuronal dynamics during attentional switching. 3) Determine the role of projection-specific PFC neurons targeting sensory and motor regions during this behaviour.