Cholinergic modulation of exploration in rats performing a spatial memory task.

Spatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Studies of rearing onto hind legs, a representative exploratory behavior, suggest that acetylcholine release promotes rearing. Here, to test this hypothesis, we tracked rearing while optogenetically modulating the activity of choline acetyltransferase containing (i.e., acetylcholine producing) neurons of the medial septum in rats performing a spatial working memory task (n=9 rats). The cholinergic neurons were optogenetically inhibited using halorhodopsin for the duration that rats occupied two of the four open arms during the study phase of an 8-arm radial arm maze win-shift task. Comparing rats' behavior in the two arm types showed that rearing frequency was not changed but the average duration of rearing epochs became significantly longer, and the total distance traveled increased in arms wherein the cholinergic neurons were inhibited. This effect on rearing and locomotion was only observed when the optogenetic inhibition was performed during the study phase. Inhibiting the cholinergic neurons during the holding phase prior to trial onset had no significant effect on any metrics tested. These results indicate that cholinergic neurons in the medial septum have a context dependent effect on exploration, do not promote rearing directly, but may facilitate the rapid encoding of information while rearing.