CHISHIKI

Drug Discovery

Decoding the activity of acetylcholine in memory formation and opportunities for drug discovery

By Sosei Heptares | Sep 16, 2021

Summary

A research collaboration between the University of Bristol’s Centre for Synaptic Plasticity and Sosei Heptares has identified specific drug targets within neural circuits in the brain that encode memories, paving the way for significant advances in the treatment of a broad spectrum of brain disorders.

The findings, published in Nature Communications, identify specific receptors for the neurotransmitter acetylcholine that re-route information flowing through memory circuits in the hippocampus region of the brain.

Acetylcholine is released in the brain during learning and is critical for the acquisition of new memories. Loss of memory is a core feature of many neurological and psychiatric disorders including Alzheimer’s disease and schizophrenia. Current treatment options for memory loss are very limited and the search for safe and effective drug therapies has, until now, had limited success.

The discovery of specific receptor targets that have the potential to provide the positive effects on memory and cognition, while avoiding the negative effects is promising and is the basis of Sosei Heptares’ selective muscarinic agonist programme.

Press release

Abstract

Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits,’ by Palacios-Filardo, J., Udakis, M., Brown, G. A., Tehan, B. G., Congreve, M. S., Nathan, P. J., Brown, A. J. H. & Mellor, J. R. (2021) in Nature Communications.

This work was supported by the Wellcome Trust and BBSRC.

Abstract