Abstract
The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and essential for attention-dependent cognitive processes. In this study we used unilateral optogenetic silencing of the LC in an attentional set-shifting task (ASST) to evaluate the influence of the LC on prefrontal cortex-dependent functions in mice. We expressed the halorhodopsin eNpHR 3.0 to reversibly silence LC activity during task performance, and found that silencing selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired, suggesting an involvement of the medial prefrontal cortex (mPFC) and the orbitofrontal cortex. In contrast, those parts of the task that are less dependent on cognitive flexibility, i.e., compound discrimination (CD) and the intra-dimensional shifts (IDS) were not affected. Furthermore, attentional set formation was unaffected by LC silencing. Our results therefore suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks.
Highlights
The Attentional Set Shifting Task (ASST) as an animal analog of the ID/ED task was designed to dissociate between two categories of frontocortical based kinds of behavioral flexibility in rodents: reversal learning and set shifting (Birrell and Brown, 2000)
The influence of optogenetic silencing on locomotion was measured by total distance and time spent inactive
Noradrenergic projections to the prefrontal cortex (PFC) might be critical for the ability to rapidly switch attention between stimuli and stimulus categories, leading to cognitive flexibility (Lapiz et al, 2007; Tait et al, 2007; McGaughy et al, 2008)
Summary
The Attentional Set Shifting Task (ASST) as an animal analog of the ID/ED task was designed to dissociate between two categories of frontocortical based kinds of behavioral flexibility in rodents: reversal learning and set shifting (Birrell and Brown, 2000). The ASST requires animals to initially learn a rule and form an “attentional set” within the same stimulus dimension before an extradimensional shift (EDS) is performed. Since attentional set shifting depends on successful prior formation of an attentional set, the task was designed with internal construct validation (Young et al, 2010) by recording the performance as a ratio of EDS and last IDS trials. If this ratio exceeds one, sufficient set formation can be assumed (Garner et al, 2006; Bissonette et al, 2008)
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