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

Abstract

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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