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Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task

View Article: PubMed Central

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.

No MeSH data available.


Related in: MedlinePlus

Experimental Setup. (A) Size and shape of the ASST box. The mouse was placed in the waiting compartment, the door was removed and the mouse allowed access to choice compartments. (B) Optical Setup. The mouse was connected to a fiber optic cable (FOC) that was connected to a fiber optic rotary joint (FRJ). Light was generated by a PC-controlled laser. (C) Example image of mouse in the box during control light illumination. (D) Table of odors and materials used for the different stages of the ASST: M1and2: wood pellets of different size, M3and4: aluminum foil pellets of different size, M5and6: cat litter of different size, M7and8: bark mulch of different size, M9and10: silica gel of different size, M11and12: plastic pellets of different size, M13and14: nuts and bolts, M15and16: metal shucks of different size, M17and18: gum Arabic of different size. Different olfactory stimuli were offered by various sweet dried herbs: O1, oregano; O2, parsley; O3, marjoram; O4, basil; O5, rosemary; O6, dill; O7, whitethorn; O8, stinging nettle; O9, lemon balm; O10, thyme; O11, ribgrass; O12, chamomile; O13, chives; O14, savory; O15, yarrow; O16, lime; O17, fennel; O18, mint.
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Figure 1: Experimental Setup. (A) Size and shape of the ASST box. The mouse was placed in the waiting compartment, the door was removed and the mouse allowed access to choice compartments. (B) Optical Setup. The mouse was connected to a fiber optic cable (FOC) that was connected to a fiber optic rotary joint (FRJ). Light was generated by a PC-controlled laser. (C) Example image of mouse in the box during control light illumination. (D) Table of odors and materials used for the different stages of the ASST: M1and2: wood pellets of different size, M3and4: aluminum foil pellets of different size, M5and6: cat litter of different size, M7and8: bark mulch of different size, M9and10: silica gel of different size, M11and12: plastic pellets of different size, M13and14: nuts and bolts, M15and16: metal shucks of different size, M17and18: gum Arabic of different size. Different olfactory stimuli were offered by various sweet dried herbs: O1, oregano; O2, parsley; O3, marjoram; O4, basil; O5, rosemary; O6, dill; O7, whitethorn; O8, stinging nettle; O9, lemon balm; O10, thyme; O11, ribgrass; O12, chamomile; O13, chives; O14, savory; O15, yarrow; O16, lime; O17, fennel; O18, mint.

Mentions: The odors consisted of commercially available household spices mixed into the digging material (odors and materials used in each trial are tabulated in Figure 1D). Digging material always contained a small amount of reward powder to preclude an olfactory-guided search for the reward itself.


Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task
Experimental Setup. (A) Size and shape of the ASST box. The mouse was placed in the waiting compartment, the door was removed and the mouse allowed access to choice compartments. (B) Optical Setup. The mouse was connected to a fiber optic cable (FOC) that was connected to a fiber optic rotary joint (FRJ). Light was generated by a PC-controlled laser. (C) Example image of mouse in the box during control light illumination. (D) Table of odors and materials used for the different stages of the ASST: M1and2: wood pellets of different size, M3and4: aluminum foil pellets of different size, M5and6: cat litter of different size, M7and8: bark mulch of different size, M9and10: silica gel of different size, M11and12: plastic pellets of different size, M13and14: nuts and bolts, M15and16: metal shucks of different size, M17and18: gum Arabic of different size. Different olfactory stimuli were offered by various sweet dried herbs: O1, oregano; O2, parsley; O3, marjoram; O4, basil; O5, rosemary; O6, dill; O7, whitethorn; O8, stinging nettle; O9, lemon balm; O10, thyme; O11, ribgrass; O12, chamomile; O13, chives; O14, savory; O15, yarrow; O16, lime; O17, fennel; O18, mint.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631833&req=5

Figure 1: Experimental Setup. (A) Size and shape of the ASST box. The mouse was placed in the waiting compartment, the door was removed and the mouse allowed access to choice compartments. (B) Optical Setup. The mouse was connected to a fiber optic cable (FOC) that was connected to a fiber optic rotary joint (FRJ). Light was generated by a PC-controlled laser. (C) Example image of mouse in the box during control light illumination. (D) Table of odors and materials used for the different stages of the ASST: M1and2: wood pellets of different size, M3and4: aluminum foil pellets of different size, M5and6: cat litter of different size, M7and8: bark mulch of different size, M9and10: silica gel of different size, M11and12: plastic pellets of different size, M13and14: nuts and bolts, M15and16: metal shucks of different size, M17and18: gum Arabic of different size. Different olfactory stimuli were offered by various sweet dried herbs: O1, oregano; O2, parsley; O3, marjoram; O4, basil; O5, rosemary; O6, dill; O7, whitethorn; O8, stinging nettle; O9, lemon balm; O10, thyme; O11, ribgrass; O12, chamomile; O13, chives; O14, savory; O15, yarrow; O16, lime; O17, fennel; O18, mint.
Mentions: The odors consisted of commercially available household spices mixed into the digging material (odors and materials used in each trial are tabulated in Figure 1D). Digging material always contained a small amount of reward powder to preclude an olfactory-guided search for the reward itself.

View Article: PubMed Central

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.

No MeSH data available.


Related in: MedlinePlus