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

Abstract

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 ␣2-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.

Interplay between Hippocampal Sharp-Wave-Ripple Events and Vicarious Trial and Error Behaviors in Decision Making

“…2G , Wilcoxon ranksum, [z=1.8, p=0.07]). Consistent with previous experiments (Johnson and Redish, 2007; Amemiya and Redish, 2016), there was decoding to both sides during VTE events, but preferentially to the chosen side on non-VTE laps ( Fig. 2H , ANOVA [n=95775], effect of region (chosen/unchosen) [df=1, F=322, p<10 −72 , η 2 =10 −3 ], effect of VTE [df=1, F=72, p<10 −17 , η 2 =10 −3 ], interaction [df=1,F=142, p< 10 −32 ,η 2 =10 −3 ]).…”

“…2H , ANOVA [n=95775], effect of region (chosen/unchosen) [df=1, F=322, p<10 −72 , η 2 =10 −3 ], effect of VTE [df=1, F=72, p<10 −17 , η 2 =10 −3 ], interaction [df=1,F=142, p< 10 −32 ,η 2 =10 −3 ]). This suggests that on laps in which the rats ran ballistically through the choice point (not showing VTE), they knew their target goal before arriving at the choice point, and the hippocampal sequences preferentially reflected only the chosen goal (Wikenheiser and Redish, 2015b; Amemiya and Redish, 2016). However, consistent with previous work (Johnson and Redish, 2007; Amemiya and Redish, 2016), on VTE laps, the hippocampal sequences were more equally divided between the two options.…”

“…This behavior ( vicarious trial and error , VTE) occurs during high uncertainty (Gardner et al, 2013; Schmidt et al, 2013; Redish, 2016), which would necessitate the exploration of future options. VTE has thus been suggested to provide a measure of uncertainty, and theta sequences during VTE may provide a neural substrate for the internal exploration of those possible future options (Johnson and Redish, 2007; Amemiya and Redish, 2016; Redish, 2016). …”

Vicarious trial and error

“…It is not known what effect clonidine has on theta sequences, but new data suggest that it limits the search process to a single path, even during VTE events 94 . This mentally searched path is the one that gets chosen by the rat 94 .…”

“…It is not known what effect clonidine has on theta sequences, but new data suggest that it limits the search process to a single path, even during VTE events 94 . This mentally searched path is the one that gets chosen by the rat 94 . A plausible explanation for the reduction in VTE following clonidine exposure is that clonidine drives the animal into the planning stage, in which it mentally explores only a single option and thus does not spend as much time expressing VTE.…”