Acetylcholine and the complex interdependence of memory and attention

Long-standing theories propose that acetylcholine biases memory by slowly shifting hippocampal dynamics to favor encoding or retrieval. However, recent characterizations of acetylcholine functions across multiple spatiotemporal scales suggest that its mnemonic influence is both broader in space, coordinating networks of regions, and narrower in time, having precisely timed consequences, than traditionally thought. Integrating this work, we review evidence for synchronous acetylcholine release across the hippocampus and neocortex, which could favor the encoding of attended and well -represented content during high-cholinergic states. Conversely, we propose that lower acetylcholine levels thought to benefit spontaneous hippocampal retrieval conflict with the high cortical levels necessary for attention-dependent aspects of recollection. We propose that rapid cholinergic mechanisms and neural oscillations may resolve these conflicting retrieval demands.