Cholinergic Dynamics in the Septo-hippocampal System Provide Phasic Multiplexed Signals for Spatial Novelty and Correlate with Behavioral States.

Abstract

In the hippocampal formation, cholinergic modulation from the medial septum/diagonal band of Broca is known to correlate with the speed of an animal's movements at subsecond timescales and also supports spatial memory formation. Yet, the extent to which subsecond cholinergic dynamics, if at all, align with transient behavioral and cognitive states supporting the encoding of novel spatial information remains unknown. In this study, we used fiber photometry to record the temporal dynamics in the population activity of septo-hippocampal cholinergic neurons at subsecond resolution during a hippocampus-dependent object location memory task using ChAT-Cre mice of both sexes. Using a linear mixed-effects model, we quantified the extent to which cholinergic dynamics were explained by changes in movement speed; behavioral states such as locomotion, grooming, and rearing; and hippocampus-dependent cognitive states such as recognizing a novel location of a familiar object. The data show that cholinergic dynamics contain a multiplexed code of fast and slow signals (1) coding for the logarithm of movement speed at subsecond timescales, (2) providing a phasic spatial novelty signal during the brief periods of exploring a novel object location, and (3) coding for recency of environmental change at a seconds-long timescale. Furthermore, behavioral event-related phasic cholinergic activity demonstrates that fast cholinergic transients correlate with a switch in cognitive and behavioral states. These findings enhance understanding of the mechanisms by which cholinergic modulation contributes to the coding of movement speed and encoding of novel spatial information.