Modulation of speed-dependent acetylcholine release in the hippocampus by spatial task engagement

Acetylcholine (ACh) plays important roles in memory encoding and attention in the hippocampus. However, changes in ACh signaling patterns during different neural and behavioral states remain poorly understood. Here, we used a genetically encoded ACh sensor and multi-plane, dual-color two-photon microscopy to establish the ACh signaling patterns in hippocampal CA1 of mice performing spatial behaviors. We observed spatially homogeneous signaling across volumes spanning hundreds of microns, which was positively correlated with locomotion speed. In novel environments, there was an increase in release persisting for dozens of laps while maintaining a positive speed correlation. When mice voluntarily disengaged, the magnitude of the speed-correlated release decreased, and this was accompanied by reduced place cell numbers and less precise place maps. Administration of scopolamine mimicked the effects of voluntary disengagement in terms of behavior and place cell metrics. These findings establish behaviorally correlated ACh signaling patterns in the hippocampus.