Manipulating Decisiveness in Decision Making: Effects of Clonidine on Hippocampal Search Strategies

摘要

Decisiveness is the ability to commit to a decision quickly and efficiently; in contrast, indecision entails the repeated consideration of multiple alternative possibilities. In humans, the α2-adrenergic receptor agonist clonidine increases decisiveness in tasks that require planning through unknown neural mechanisms. In rats, indecision is manifested as reorienting behaviors at choice points (vicarious trial and error [VTE]), during which hippocampal representations alternate between prospective options. To determine whether the increase in decisiveness driven by clonidine also entails changes in hippocampal search processes, we compared the effect of clonidine on spatial representations in hippocampal neural ensembles as rats passed through a T-shaped decision point. Consistent with previous experiments, hippocampal representations reflected both chosen and unchosen paths during VTE events under saline control conditions. Also, consistent with previous experiments, hippocampal representations reflected the chosen path more than the unchosen path when the animal did not show VTE at the choice point. Injection of clonidine suppressed the spatial representation of the unchosen path at the choice point on VTE laps and hastened the differentiation of spatial representations of the chosen path from the unchosen path on non-VTE laps to appear before reaching the choice point. These results suggest that the decisiveness seen under clonidine is due to limited exploration of potential options in hippocampus, and suggest novel roles for noradrenaline as a modulator of the hippocampal search processes.>SIGNIFICANCE STATEMENT Clonidine, an α2-adrenergic receptor agonist, which decreases the level of noradrenaline in vivo, has an interesting effect in humans and other animals: it makes them more decisive. However, the mechanisms by which clonidine makes them more decisive remain unknown. Researchers have speculated that clonidine limits the amount of mental search that subjects do when planning options. We test this hypothesis by measuring the mental search strategy in rats through hippocampal recordings. We find that clonidine limits the options searched by rats, suggesting that noradrenaline also plays a role in balancing exploration and exploitation in internally simulated behaviors, similar to its role in balancing exploration and exploitation in external behaviors.