title: Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task.
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.
authors.affiliation: Department of Neurology, University of Magdeburg Magdeburg, Germany ; Systems Physiology of Learning, Leibniz Institute of Neurobiology Magdeburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Janitzky
authors.affiliation: Systems Physiology of Learning, Leibniz Institute of Neurobiology Magdeburg, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lippert
authors.affiliation: Systems Physiology of Learning, Leibniz Institute of Neurobiology Magdeburg, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Engelhorn
authors.affiliation: Systems Physiology of Learning, Leibniz Institute of Neurobiology Magdeburg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tegtmeier
authors.affiliation: Systems Physiology of Learning, Leibniz Institute of Neurobiology Magdeburg, Germany ; Center for Behavioral Brain Sciences Magdeburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Goldschmidt
authors.affiliation: Department of Neurology, University of Magdeburg Magdeburg, Germany ; Systems Physiology of Learning, Leibniz Institute of Neurobiology Magdeburg, Germany ; Center for Behavioral Brain Sciences Magdeburg, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Systems Physiology of Learning, Leibniz Institute of Neurobiology Magdeburg, Germany ; Center for Behavioral Brain Sciences Magdeburg, Germany ; Systems Physiology, Institute of Biology, University of Magdeburg Magdeburg, Germany.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Ohl
keywords: B6.Cg-Tg(Th-cre)1Tmd/J hemizygous mice; attentional set-shifting task; cognitive flexibility; extra-dimensional set-shifting; halorhodopsin; locus coeruleus; optogenetics; prefrontal cortex