Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance.

McGaughy, Jill; Sandstrom, Michael I; Ruland, Shane; Bruno, John P.; Sarter, Martin

doi:10.1037/0735-7044.111.3.646

Cited by 36 publications

(23 citation statements)

References 31 publications

(66 reference statements)

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“…Cortical NA levels also increased in contingent subjects, although there was no indication on either day of testing that this response was specifically related to task performance. This is consistent with previous lesion studies showing a lack of effect of cortical NA depletion on baseline performance on this task (Carli et al, 1983;Cole and Robbins, 1992) as well as other attentional paradigms (McGaughy et al, 1997). In contrast, performance on the five-choice serial reaction time task produced sustained increases in cortical ACh efflux.…”

Section: Discussionsupporting

confidence: 81%

Distinct Changes in Cortical Acetylcholine and Noradrenaline Efflux during Contingent and Noncontingent Performance of a Visual Attentional Task

et al. 2001

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Optimization of cognitive processing may depend on specific and distinct functions of the cortical cholinergic and noradrenergic systems. This investigation dissociates functions of cortical acetylcholine (ACh) and noradrenaline (NA) in arousal and visual attention by simultaneously measuring ACh and NA efflux in the rat prefrontal cortex during sustained attentional performance. The five-choice serial reaction time task was used to provide a continuous assessment of visuospatial attention. Previous studies using this task have established a critical role for the cortical cholinergic system in the detection of visual targets. However, selective lesions of the locus coeruleus noradrenergic system impair performance only when additional attentional demands are placed on the subject by distractors or temporally unpredictable targets. To test the hypothesis that the cortical noradrenergic system is particularly sensitive to novel task contingencies, we also assessed NA and ACh efflux in rats that been trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished. Cortical ACh efflux showed a robust and task-related increase during established contingent performance. This response was significantly attenuated in noncontingent subjects, although it still exceeded pretask values. In contrast, NA efflux only increased transiently in contingent subjects after task onset but showed sustained elevations in noncontingent subjects on the first day when contingencies were changed. These data also implicate cortical ACh in aspects of attentional functioning but highlight a specific involvement of the cortical noradrenergic system in detecting shifts in the predictive relationship between instrumental action and reinforcement.

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Section: Discussionsupporting

confidence: 81%

Distinct Changes in Cortical Acetylcholine and Noradrenaline Efflux during Contingent and Noncontingent Performance of a Visual Attentional Task

et al. 2001

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“…NE-LX animals would often fail to explore the other stimulus attribute in the test of ED for many trials. It is unlikely that the NE-LX rats suffer from a loss of sustained attention as rats with larger NE lesions are unimpaired in standard tests of sustained attention (McGaughy et al, 1997;Milstein et al, 2007). Unpublished data show that similar noradrenergic lesions of the IL/PL produce an insensitivity to cross-modal distraction in a visual sustained, attention task (Newman et al, 2006) supporting the hypothesis that the attentional focus of these rats is abnormally narrow and that they persist in responding to a stimulus that previously predicted reinforcement.…”

Section: Hypoactive or Hyperactive Ne?mentioning

confidence: 49%

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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“…This means that the decrement is not associated with decreased activity of a serotonergicnoradrenergic system or, alternatively, that the noradrenaline reuptake blocking properties of venlafaxine are not strong enough. Although this is the only human study perfomed in vivo that points in this direction, there is abundant evidence from animal studies that noradrenaline is not the critical neurotransmitter specifically associated with the maintenance of vigilance (Delagrange et al, 1993;McGaughy et al, 1997). It is more likely that noradrenaline is associated with phasic arousal, whereas dopamine is more likely to be associated with a tonic readiness to respond (Pribram and McGuinness, 1975;Robbins, 1997).…”

Section: Vigilancementioning

confidence: 95%

Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment

et al. 2005

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Subchronic treatment with the selective serotonergic reuptake inhibitors (SSRIs) fluoxetine, venlafaxine and paroxetine, but not sertraline, were previously shown to specifically impair vigilance performance. The current study was designed to compare the vigilance effects of subchronic treatment with the SSRIs sertraline and citalopram in healthy volunteers, according to a placebo-controlled, double-blind, three-way cross-over design. Twenty-four healthy subjects, aged 30-50 years, of whom 21 completed the study, underwent three treatment periods of 2 weeks in which they received sertraline (50 mg on days 1-8, 100 mg on days 8-15), citalopram (20 mg on days 1-8, 40 mg on days 8-15) and placebo. Treatment periods were separated by 14 days washout periods. Vigilance performance was assessed through a 45-min Mackworth Clock Test at days 1, 8 and 15 of each treatment period. It was found that citalopram impaired vigilance performance acutely after the first 20 mg dose and subchronically after 40 mg daily doses. By contrast, no vigilance impairment was found during sertraline treatment. Sertraline is the only SSRI studied so far with no detrimental effects on vigilance. This may be due to the affinity of sertraline for the dopamine reuptake site. Because citalopram is the most specific SSRI showing this effect, it is concluded that the SSRI-induced decrement of vigilance performance is specifically associated with serotonergic reuptake inhibition.

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Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance.

Cited by 36 publications

References 31 publications

Distinct Changes in Cortical Acetylcholine and Noradrenaline Efflux during Contingent and Noncontingent Performance of a Visual Attentional Task

Distinct Changes in Cortical Acetylcholine and Noradrenaline Efflux during Contingent and Noncontingent Performance of a Visual Attentional Task

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

Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment

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