Inhibition in the Periaqueductal Gray (360G-Wellcome-203729_Z_16_A)

Deciding which action to take, such as whether to cross a busy road, is a critical survival skill. Making decisions requires integrating complex information and identifying the cellular mechanisms of this process is critical for understanding how the brain computes decisions. In this project will investigate neurons that control defensive decisions in mice and focus on inhibitory neurons in the midbrain Periaqueductal Grey (PAG), which have the ability to veto defensive behaviours.The first main goal of the project is to use electrophysiological and advanced molecular techniques, such as RNA sequencing and gene knock-down, to identify the genes and ion channels that control the firing of PAG inhibitory neurons. The second goal is to determine key regulators of the activity of these neurons, in particular neuromodulators and long-range synaptic connections from other brain areas, using techniques such as optogenetics in combination with behavioural assays that exploit the innate defensive behaviours of mice. The results of this work will reveal new the biophysical principles that drive firing in a key population controlling a critical behavioural decision, and provide an entry point for understanding how pathological states such as anxiety lead to maladaptive decisions.