Phase Model Analysis of the Effect of Acetylcholine on the Neural Synchrony in Hippocampal Networks

Abstract

Neural assemblies—transiently coordinated groups of neurons—are observed in the hippocampus and are thought to underlie the encoding and consolidation of episodic memories. Acetylcholine (ACh), a key neuromodulator, plays a critical role in learning and memory and has been implicated in neurodegenerative disorders involving hippocampal dysfunction. A well-supported hypothesis suggests that high levels of ACh during active exploration and rapid eye movement (REM) sleep promote memory encoding, while low levels during quiet waking and slow-wave sleep (SWS) support memory consolidation.

In this study, we examine the bidirectional role of ACh in modulating neural assembly formation through its effect on neural synchrony in the CA3 region of the hippocampus. We construct a computational model of a network of excitatory pyramidal neurons, each equipped with a slow, voltage-dependent, non-inactivating potassium current (M-current), which is downregulated in the presence of ACh. Neural assemblies are modelled mathematically as cluster solutions—special types of phase-locked states. Using a phase model reduction of a pair of weakly coupled neurons, we analyze the existence and stability of cluster solutions that may emerge in larger networks equipped with all-to-all globally homogeneous, symmetric distance-dependent and nearest-neighbours coupling architectures.

Our results suggest that ACh shapes assembly formation by modulating network dynamics in CA3. Under low ACh conditions, the network tends to fully synchronize, whereas high ACh levels enable the emergence of multiple stable cluster states, allowing for distinct patterns of activity associated with memory encoding. These findings propose a mechanism by which ACh regulates transitions in hippocampal network states, supporting distinct stages of memory formation.