Molecular mechanisms determining the polarised synaptic distribution and molecular function of the retrograde endocannabinoid signalling system

Cannabis has been used as a medicine for thousands of years. Chemicals in cannabis work by activating a protein in the brain called cannabinoid receptor 1 (CB1R), which is part of a network of proteins called the endocannabinoid signalling system (ECS). The ECS dampens-down brain activity by reducing the amount of neurotransmitter released at connections between nerve cells called synapses. This is a vitally important feedback loop that prevents synaptic activity from spiralling out of control. We want to explore the biochemical 'nuts and bolts' of the cellular machinery that controls proteins critical for ECS function. This will provide important new information on how the ECS works, and how it can go wrong. Because a major role of the ECS is to prevent excessive activity which can kill nerve cells, our findings could eventually lead to new ways of enhancing ECS signalling to protect nerve cells in conditions like epilepsy.