Acetylcholine Release Coordinated Brain-wide To Optimise Memory Encoding

A chemical signal released across the brain in response to attention demanding or arousing situations has been identified new research investigating how heightened attention improves our mental capacity.

The findings shed light on how current drugs used in the treatment of Alzheimer’s, designed to boost this chemical signal, counter the symptoms of dementia. The results could also lead to new ways of enhancing cognitive function to counteract the effects of diseases such as Alzheimer’s and schizophrenia, as well as enhancing memory in healthy people.

The team of researchers, from the Universities of Bristol and Maynooth, in collaboration with pharmaceutical company Eli Lilly & Company, studied how the release of the chemical acetylcholine fluctuates during the day but found that the release is at its highest when the brain is engaged with more challenging mental tasks. The fluctuations are coordinated across the brain indicating a brain-wide signal to increase mental capacity with specific spikes in acetylcholine release occurring at particularly arousing times such as gaining reward.

Acetylcholine Release

Professor Jack Mellor, lead researcher from Bristol’s Centre for Synaptic Plasticity, said:

“These findings are about how brain state is regulated and updated on a rapid basis to optimise the encoding of memory and cognitive performance. Many current and future drug therapies for a wide range of brain disorders including Alzheimer’s and schizophrenia are designed to target chemical systems such as acetylcholine so understanding when they are active and therefore how they function will be crucial for their future development and clinical use.”

Electrochemical enzyme-based biosensors were used to simultaneously measure the release acetylcholine in the prefrontal cortex and hippocampus of mice. Previous studies measuring acetylcholine release employed microdialysis, juxtacellular recording or calcium imaging and optogenetic techniques, but due to the limitations of these methods, the precise timing and location of acetylcholine release have remained unclear.

The researchers found that release on both tonic and phasic timescales is remarkably coordinated between brain regions and dependent on behavioral state.

Acetylcholine release was at it’s highest maximal during training on a rewarded working memory task. Also, it was found that tonic release increase during REM sleep predicted subsequent wakefulness.

The work was supported by Eli Lilly and Company, Maynooth University, the Biotechnology and Biological Sciences Research Council, and Wellcome Trust.

Leonor M. Teles-Grilo Ruivo, et al
Coordinated acetylcholine release in prefrontal cortex and hippocampus is associated with arousal and reward on distinct timescales
Cell Reports DOI: