Lesions of the dorsal noradrenergic bundle impair attentional set‐shifting in the rat

Tait, David S.; Brown, Valerie J.; Farovik, Anja; Theobald, David E. H.; Dalley, Jeffrey W.; Robbins, Trevor W.

doi:10.1111/j.1460-9568.2007.05612.x

Cited by 154 publications

(135 citation statements)

References 46 publications

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“…Our findings are in line with recent findings from Robbins and colleagues (Tait et al, 2007) who showed that lesions of the dorsal noradrenergic bundle produce more severe loss of noradrenergic innervation of the cortex and also impair ED. The current findings differ slightly from results produced by Lapiz and Morilak (2006) that failed to find impairments in any aspect of the task following systemic administration of clonidine, an α2 autoreceptor agonist which decreases NE levels.…”

Section: Hypoactive or Hyperactive Ne?supporting

confidence: 83%

“…A NE reuptake inhibitor restores normal performance in NE-LX rats but impairs performance of normal rats (Newman et al, 2008). Based on these data, we hypothesize that the attentional deficits in the current study result from a decrease in levels of cortical NE but concurrent microdialysis during the behavioral test would be useful in determining how NE levels correlate with performance.Our findings are in line with recent findings from Robbins and colleagues (Tait et al, 2007) who showed that lesions of the dorsal noradrenergic bundle produce more severe loss of noradrenergic innervation of the cortex and also impair ED. The current findings differ slightly from results produced by Lapiz and Morilak (2006) that failed to find impairments in any aspect of the task following systemic administration of clonidine, an α2 autoreceptor agonist which decreases NE levels.…”

supporting

confidence: 83%

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Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

2008

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Both norepinephrine and acetylcholine have been shown to be critically involved in mediating attention but there remains debate about whether they serve similar or unique functions. Much of what is known about the role of these neurochemicals in cognition is based on manipulations done at the level of the cell body but these findings are difficult to reconcile with data regarding the unique contribution of cortical subregions, e.g. the dorsolateral prefrontal cortex, to attention. In the current study, we directly compared the effects of noradrenergic and cholinergic deafferentation of the rat medial prefrontal cortex, the homologue of primate dorsolateral prefrontal cortex, using an intradimensional/extradimensional attentional set shifting task, a task previously shown to be able to dissociate the function of the primate dorsolateral prefrontal cortex from orbitofrontal cortex. We found that noradrenergic, but not cholinergic, deafferentation produces specific impairments in the ability to shift attentional set. We also clarified the nature of the attentional deficits by assessing the ability of rats to disregard irrelevant stimuli. Noradrenergic lesions did not alter the ability of rats to ignore irrelevant stimuli, suggesting that the attentional deficit results from an overly focused attentional state that retards learning that a new stimulus dimension predicts reward. KeywordsDBH saporin; 192 IgG saporin; infralimbic/prelimbic cortices; selective attention Studies aimed at understanding the neurochemical basis of attention have found that both norepinephrine (NE) and acetylcholine (ACh) mediate aspects of attention (McGaughy and Sarter, 1995b;McGaughy et al., 1996;Rajkowski et al., 2004;Milstein et al., 2007) but some conditions dissociate the functions of these systems. Yu and Dayan (2005) hypothesize that NE mediates unexpected uncertainty while ACh mediates expected uncertainty. In other words, there exists some known ambiguity in many attentional situations, e.g. spatial or temporal unpredictability of targets, and variability in perceptual attributes of target (Chiba et al., 1995;McGaughy and Sarter, 1995a;Bucci et al., 1998;McGaughy et al., 2002;Maddux et al., 2007). After acquisition, this uncertainty though not predictable is known, expected, and requires ACh Dayan, 2002, 2005). Additionally, unexpected uncertain events may occur, e.g. changes in reinforcement contingencies in a well-learned task, and recruit NE (Robbins, 2000;Dalley et al., 2001; Sara, 2004, 2005;Dalley et al., 2004;Yu and Dayan, 2005 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThough these frameworks are useful there remains ambiguity about the attentional situations that require ACh and those that require NE. This ambiguity may result from a reliance on data obtained from manipulations of the cell bodies of these systems (Aston-Jones et al., 1994, 2000McGaughy et al., 1996McGaughy et al., , 2002. Both NE and ACh innervate much of the neocortical mantle so previous frameworks posited a unita...

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Section: Hypoactive or Hyperactive Ne?supporting

confidence: 83%

supporting

confidence: 83%

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

2008

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“…Switching between abstract rules in these prior task-switching studies might be similar to extradimensional shifting in the context of the ID/ED paradigm. Indeed, findings from work with experimental animals have shown that EDS is sensitive to excitotoxic and neurochemical lesions in the pFC (McGaughy, Ross, & Eichenbaum, 2008;Tait et al, 2007;Crofts et al, 2001;Birrell & Brown, 2000;Roberts et al, 1994) and in the parietal cortex (Fox, Barense, & Baxter, 2003) but not in the striatum (Crofts et al, 2001;Collins, Wilkinson, Everitt, Robbins, & Roberts, 2000; for a review, see Robbins, 2007). In fact, the present performance pattern strikingly resembles that seen after catecholamine lesions in the pFC of nonhuman primates (Crofts et al, 2001).…”

Section: Discussionsupporting

confidence: 55%

Top–Down Attentional Control in Parkinson's Disease: Salient Considerations

Cools

Rogers

Barker³

et al. 2010

Journal of Cognitive Neuroscience

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Abstract■ Cognitive dysfunction in Parkinsonʼs disease (PD) has been hypothesized to reflect a failure of cortical control. In keeping with this hypothesis, some of the cognitive deficits in PD resemble those seen in patients with lesions in the lateral pFC, which has been associated with top-down attentional control. However, there is no direct evidence for a failure of top-down control mechanisms in PD. Here we fill this gap by demonstrating disproportionate control by bottom-up attention to dimensional salience during attentional set shifting. Patients needed significantly more trials to criterion than did controls when shifting to a low-salient dimension while, remarkably, needing significantly fewer trials to criterion than did controls when shifting to a highsalient dimension. Thus, attention was captured by bottom-up attention to salient information to a greater extent in patients than in controls. The results provide a striking reinterpretation of prior set-shifting data and provide the first direct evidence for a failure of top-down attentional control, resembling that seen after catecholamine depletion in the pFC. ■

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“…Our laboratory and others have demonstrated that NE facilitates ED set-shifting in the mPFC (Lapiz and Morilak, 2006;Tait et al, 2007;Bondi et al, 2008;McGaughy et al, 2008). Further, we showed recently that increasing Figure 5 Effects of noradrenergic receptor blockade in mPFC during CUS, followed by an acute microinjection into the mPFC immediately prior to testing on the ED task.…”

Section: Discussionmentioning

confidence: 86%

Too Much of a Good Thing: Blocking Noradrenergic Facilitation in Medial Prefrontal Cortex Prevents the Detrimental Effects of Chronic Stress on Cognition

Jett

Morilak

2012

Neuropsychopharmacol

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Cognitive impairments associated with dysfunction of the medial prefrontal cortex (mPFC) are prominent in stress-related psychiatric disorders. We have shown that enhancing noradrenergic tone acutely in the rat mPFC facilitated extra-dimensional (ED) set-shifting on the attentional set-shifting test (AST), whereas chronic unpredictable stress (CUS) impaired ED. In this study, we tested the hypothesis that the acute facilitatory effect of norepinephrine (NE) in mPFC becomes detrimental when activated repeatedly during CUS. Using microdialysis, we showed that the release of NE evoked in mPFC by acute stress was unchanged at the end of CUS treatment. Thus, to then determine if repeated elicitation of this NE activity in mPFC during CUS may have contributed to the ED deficit, we infused a cocktail of a 1 -, b 1 -, and b 2 -adrenergic receptor antagonists into the mPFC prior to each CUS session, then tested animals drug free on the AST. Antagonist treatment prevented the CUS-induced ED deficit, suggesting that NE signaling during CUS compromised mPFC function. We confirmed that this was not attributable to sensitization of adrenergic receptor function following chronic antagonist treatment, by administering an additional microinjection into the mPFC immediately prior to ED testing. Acute antagonist treatment did not reverse the beneficial effects of chronic drug treatment during CUS, nor have any effect on baseline ED performance in chronic vehicle controls. Thus, we conclude that blockade of noradrenergic receptors in mPFC protected against the detrimental cognitive effects of CUS, and that repeated elicitation of noradrenergic facilitatory activity is one mechanism by which chronic stress may promote mPFC cognitive dysfunction.

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Lesions of the dorsal noradrenergic bundle impair attentional set‐shifting in the rat

Cited by 154 publications

References 46 publications

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

Top–Down Attentional Control in Parkinson's Disease: Salient Considerations

Too Much of a Good Thing: Blocking Noradrenergic Facilitation in Medial Prefrontal Cortex Prevents the Detrimental Effects of Chronic Stress on Cognition

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