Chemogenetics Reveal an Anterior Cingulate-Thalamic Pathway for Attending to Task-Relevant Information.

Emma J Bubb,John P Aggleton,Andrew J D Nelson,Shane M O'Mara

doi:10.1093/cercor/bhaa353

Abstract

In a changing environment, organisms need to decide when to select items that resemble previously rewarded stimuli and when it is best to switch to other stimulus types. Here, we used chemogenetic techniques to provide causal evidence that activity in the rodent anterior cingulate cortex and its efferents to the anterior thalamic nuclei modulate the ability to attend to reliable predictors of important outcomes. Rats completed an attentional set-shifting paradigm that first measures the ability to master serial discriminations involving a constant stimulus dimension that reliably predicts reinforcement (intradimensional-shift), followed by the ability to shift attention to a previously irrelevant class of stimuli when reinforcement contingencies change (extradimensional-shift). Chemogenetic disruption of the anterior cingulate cortex (Experiment 1) as well as selective disruption of anterior cingulate efferents to the anterior thalamic nuclei (Experiment 2) impaired intradimensional learning but facilitated 2 sets of extradimensional-shifts. This pattern of results signals the loss of a corticothalamic system for cognitive control that preferentially processes stimuli resembling those previously associated with reward. Previous studies highlight a separate medial prefrontal system that promotes the converse pattern, that is, switching to hitherto inconsistent predictors of reward when contingencies change. Competition between these 2 systems regulates cognitive flexibility and choice.

Highlights

IntroductionThe ability to engage in adaptive behaviors is critical to an organism’s survival
In a dynamic world, the ability to engage in adaptive behaviors is critical to an organism’s survival
Taking advantage of the anterograde transport of an adenoassociated virus expressing the inhibitory hM4Di DREADD receptor, coupled with localized infusions of the ligand within the anterior thalamic nuclei (ATN), we examined the effects of chemogentically disrupting anterior cingulate cortex (ACC) terminations within ATN on the same attentional setshifting tasks

Summary

Introduction

The ability to engage in adaptive behaviors is critical to an organism’s survival. This includes deciding when to select items that resemble consistently rewarded stimuli and when to switch to previously irrelevant stimulus types. The ability to disengage from previously rewarded response strategies depends on the integrity of prefrontal cortex. Further research with rats highlights how interactions between medial prefrontal cortex and subcortical sites support this form of behavioral flexibility (Block et al 2007; Baker and Ragozzino 2014; Dolleman-Van Der Weel et al 2019). Until recently, there has been little progress in identifying the neural circuits in rodents that support the opposing attentional mechanism, that is, the preferential processing of stimuli resembling those previously associated with important outcomes

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Discussion

Conclusion