Spatial working memory over long retention intervals: Dependence on sustained cholinergic activation in the septohippocampal or nucleus basalis magnocellularis-cortical pathways?

Abstract

Previous direct neurochemical studies of the temporal dynamics of cholinergic activation in the septohippocampal and nucleus basalis magnocellularis-cortical pathways at various stages during repeated testing of mice with selective spatial reference or working memory protocols [Durkin and Toumane (1992), Behav. Brain Res. 50,43–52] showed that the post-test durations of cholinergic activation in each pathway varied as a function of the type of memory tested and the level of task mastery. Since (i) the hippocampal formation is considered to constitute a critical component of a temporary memory buffer, and (ii) working memory items are not thought to be submitted to consolidation and permanent storage, we postulated that the duration of testing-induced cholinergic activation in the septohippocampal pathway may govern the maintenance of the working memory trace over the retention interval. In order to test directly this hypothesis C57 B1/6 mice were extensively trained (one trial/day, 25–30 days) on an identical selective working memory task to attain high levels of retention (> 80% correct), but using either 5 min (Group 1), or 60 min (Group 2) retention intervals. At various times (30s–75min) following the initial acquisition phase of the test, cholinergic activity in the hippocampus and frontal cortex was quantified using measures of high-affinity choline uptake. Whereas cholinergic activation was observed in both pathways at 30 s post-acquisition and throughout the 5 min retention interval in Group 1, the situation in Group 2 is different, activation of the septohippocampal pathway being maintained for only 15 min, while activation in the nucleus basalis magnocellularis-cortical pathway is maintained for the totality of the 1 h retention interval. The nucleus basalis magnocellularis-cortical cholinergic pathway, in addition to its role in long-term reference memory storage processes may, thus, via an intervention in the temporal encoding of information, also subsume a complementary intermediate-term buffer storage role in working memory situations requiring retention intervals in excess of 15min in mice. This secondary, “backup”, function of the nucleus basalis magnocellularis-cortical pathway would thus liberate the septohippocampal complex from its primary active role in the temporary maintenance and/or accessibility of the working memory trace in these particular cases requiring long retention intervals.