Research could refine next generation of drugs to help treat dementia

A £1.1 million grant to understand how one of the brain's key neurotransmitters called 'acetylcholine' influences brain activity has been awarded to University of Bristol researchers. The Wellcome Trust award will help scientists understand more precisely how the release of acetylcholine is changing brain cell activity to influence memory and cognition.

Acetylcholine is a chemical compound released in the brain which is known to play an important role in normal brain functions such as sleep, attention, and learning and memory. It is also one of the first neurotransmitters to be depleted in Alzheimer's disease.

Acetylcholinesterase inhibitors (drugs which act by increasing the global action of acetylcholine throughout the brain) are currently used to treat disorders such as schizophrenia and dementia hence why its research is significant in terms of its implications for future therapeutic potential. However, given these drugs' non-targeted mode of action across all areas of the brain, the efficacy of this approach is mixed, and side-effects can be common.

The five-year project, led by Dr Jack Mellor from Bristol's School of Physiology and Pharmacology in the Faculty of Medical and Veterinary Sciences, will study the precise brain areas where acetylcholine is released to find out how it affects brain cell activity and changes their ability to communicate within networks. This better understanding could help to inform and refine the development of the next generation of therapeutic cholinergic agents.

By looking at the effect of acetylcholine at the cellular level and how it affects neuronal-network activity within the hippocampus - the area within the brain which encodes and consolidates information for memory and learning - the team hope to identify specific brain areas, cell-types and receptors that are targeted by acetylcholine to affect brain function.

Dr Mellor said: "This award pulls together expertise from a number of collaborators at the University of Bristol as well as researchers from Oxford, Dublin and pharmaceutical company Eli Lilly & co. The interdisciplinary approach is exciting and we hope will lead to new insight into the role of this important neuromodulator in memory and cognitive function."