Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task
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 prefron...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2015-11-01
|
| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00286/full |
| _version_ | 1818987190425747456 |
|---|---|
| author | Kathrin eJanitzky Kathrin eJanitzky Michael eLippert Achim eEngelhorn Jürgen eGoldschmidt Jürgen eGoldschmidt Jennifer eTegtmeier Hans-Jochen eHeinze Hans-Jochen eHeinze Hans-Jochen eHeinze Frank W. Ohl Frank W. Ohl Frank W. Ohl Frank W. Ohl |
| author_facet | Kathrin eJanitzky Kathrin eJanitzky Michael eLippert Achim eEngelhorn Jürgen eGoldschmidt Jürgen eGoldschmidt Jennifer eTegtmeier Hans-Jochen eHeinze Hans-Jochen eHeinze Hans-Jochen eHeinze Frank W. Ohl Frank W. Ohl Frank W. Ohl Frank W. Ohl |
| author_sort | Kathrin eJanitzky |
| collection | DOAJ |
| description | 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 eNpHR3.0 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. |
| first_indexed | 2024-12-20T19:02:45Z |
| format | Article |
| id | doaj.art-974e6db46a284bca99ae08d8b3ab4677 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-12-20T19:02:45Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-974e6db46a284bca99ae08d8b3ab46772022-12-21T19:29:22ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532015-11-01910.3389/fnbeh.2015.00286162756Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting taskKathrin eJanitzky0Kathrin eJanitzky1Michael eLippert2Achim eEngelhorn3Jürgen eGoldschmidt4Jürgen eGoldschmidt5Jennifer eTegtmeier6Hans-Jochen eHeinze7Hans-Jochen eHeinze8Hans-Jochen eHeinze9Frank W. Ohl10Frank W. Ohl11Frank W. Ohl12Frank W. Ohl13University of MagdeburgLeibniz Institute of Neurobiology (LIN)Leibniz Institute of Neurobiology (LIN)Leibniz Institute of Neurobiology (LIN)Leibniz Institute of Neurobiology (LIN)Center for Behavioral Brain Sciences (CBBS)Leibniz Institute of Neurobiology (LIN)University of MagdeburgLeibniz Institute of Neurobiology (LIN)Center for Behavioral Brain Sciences (CBBS)University of MagdeburgLeibniz Institute of Neurobiology (LIN)Center for Behavioral Brain Sciences (CBBS)Institute of Biology, University of MagdeburgThe 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 eNpHR3.0 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.http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00286/fullLocus CoeruleusPrefrontal Cortexoptogeneticshalorhodopsincognitive flexibilityB6.Cg-Tg(Th-cre)1Tmd/J hemizygous mice |
| spellingShingle | Kathrin eJanitzky Kathrin eJanitzky Michael eLippert Achim eEngelhorn Jürgen eGoldschmidt Jürgen eGoldschmidt Jennifer eTegtmeier Hans-Jochen eHeinze Hans-Jochen eHeinze Hans-Jochen eHeinze Frank W. Ohl Frank W. Ohl Frank W. Ohl Frank W. Ohl Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task Frontiers in Behavioral Neuroscience Locus Coeruleus Prefrontal Cortex optogenetics halorhodopsin cognitive flexibility B6.Cg-Tg(Th-cre)1Tmd/J hemizygous mice |
| title | Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task |
| title_full | Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task |
| title_fullStr | Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task |
| title_full_unstemmed | Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task |
| title_short | Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task |
| title_sort | optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set shifting task |
| topic | Locus Coeruleus Prefrontal Cortex optogenetics halorhodopsin cognitive flexibility B6.Cg-Tg(Th-cre)1Tmd/J hemizygous mice |
| url | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00286/full |
| work_keys_str_mv | AT kathrinejanitzky optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT kathrinejanitzky optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT michaelelippert optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT achimeengelhorn optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT jurgenegoldschmidt optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT jurgenegoldschmidt optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT jenniferetegtmeier optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT hansjocheneheinze optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT hansjocheneheinze optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT hansjocheneheinze optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT frankwohl optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT frankwohl optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT frankwohl optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask AT frankwohl optogeneticsilencingoflocuscoeruleusactivityinmiceimpairscognitiveflexibilityinanattentionalsetshiftingtask |