Poster Z8 - Cholinergic dynamics in the septo-hippocampal system correlate with changes in cognitive and behavioral states

Introduction: In the hippocampal formation, cholinergic modulation from the medial septum/diagonal band of Broca (MSDB) is known to support the formation of spatial memories and cognitive functions that enable memory-guided navigation. However, recent experimental data in mice demonstrate that cholinergic activity correlates with the speed of movements, such as locomotion speed or head movements when the mouse is stationary.

Materials and

Methods: In this study, we used fiber photometry to record the temporal dynamics in the population activity of septo-hippocampal cholinergic projection neurons in the MSDB at sub-second resolution during an object location memory task using ChAT-Cre mice. Mice were video-tracked, and their pose and behavioral activities were classified using deep learning approaches. General linear models are employed to quantify the extent to which cholinergic dynamics in the septo-hippocampal circuitry are explained by changes in behavioral states such as locomotion, grooming, and rearing, and hippocampus-dependent cognitive states such as recognizing a novel location of a familiar object. Additionally, we are developing a toolbox in Python for analyzing fiber photometry data.

Results, Conclusions, and Discussions: Consistent with prior data, our results demonstrate a strong correlation between the activity of cholinergic neurons in the MSDB and the logarithm of the animals' running speed. Additionally, we provide evidence for reduced cholinergic modulation during grooming. The data show a trend of higher cholinergic activity, adjusted for the effects of movement speed, rearing and grooming, during the time points when the mouse is exploring a familiar object at a novel location. This finding is consistent with a long-standing hypothesis that acetylcholine supports the encoding of novel information. Lastly, we quantified the time course of changes in cholinergic activity at the start and end points of behavioral activities, after correcting for the effects of movement speed. The results suggest that fast cholinergic transients help facilitate a switch in cognitive or behavioral state. Quantifying the temporal dynamics of cholinergic modulation in hippocampal memory circuits, in relation to movement speed, behavioral activities, and cognitive tasks such as the learning and recall of object locations, will enable us to evaluate long-standing hypotheses regarding the function of cholinergic modulation for memory and exploratory behavior.

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