Functional hypotheses of the coeruleocortical noradrenergic projection: A review of recent experimentation and theory

Abstract

The behavioral function of the coeruleocortical system and the hypotheses implicating its role in mediating selective attention and behavioral inhibition to anxiogenic cues are evaluated. The diverse pattern of results produced by lesions induced by 6-hydroxydopamine on a variety of tasks (appetitive conditional discrimination, nonreversal shift, blocking, latent inhibition, distraction, taste aversion, neophobia, and conditioned emotional response) are integrated to achieve a tentative hypothesis of coeruleocortical noradrenergic function.There has been enormous interest in the functions of the nucleus locus coeruleus (LC) and its projections to the cortex via the dorsal noradrenergic bundle (DNAB) from several neurobiological perspectives. Although the nature of the afferents to the LC and the precise organization of the DNAB are still a matter for debate, it is perhaps of some functional significance that a single cell body can give rise to both ascending and descending axons innervating regions as diverse as the neocortex, hippocampus, cerebellum, and spinal cord. These peculiar features of organization suggest, for want of a better term, a rather "general" function whereby messages relayed to at least a proportion of noradrenergic (NA) cell bodies would result in the transmission of information to widespread regions, thereby influencing the special forms of processing occurring there.Although such general considerations imply rather nonspecific functions for the LC, we should like to avoid the temptation of assuming simply that this implies a role in nonspecific processes along the lines of the maintenance of cortical arousal by the reticular formation suggested originally by Hebb, Lindsley, and others. Recent neu-

Destruction of central noradrenergic neurones with DSP4 impairs the acquisition of temporal discrimination but does not affect memory for duration in a delayed conditional discrimination task

“…This finding replicates our previous observation of retarded learning of a temporal discrimination following treatment with DSP4 (Ho et al 1995). This effect is not particular to the acquisition of temporal discriminations; indeed, there is evidence that destruction of the central noradrenergic pathways impairs discrimination learning in a variety of paradigms employing visual or auditory discriminanda (Everitt et al 1983;Robbins et al 1985;Ho et al 1995), although not in tasks employing tactile or gustatory stimuli (Jarbe et al 1988). Noradrenaline depletion has been found to delay acquisition in some spatial learning tasks (Mason and Lin 1980;Archer 1982;Spyraki et al 1982;Anderson et al 1986;Langlais et al 1993;Compton et al 1995), although there have been several studies in which destruction of the noradrenergic pathways failed to affect spatial learning (Hagan et al 1983;Pisa and Fibiger 1983;Spangler et al 1990), possibly reflecting the wide variety of spatial learning paradigms that have been employed in different studies.…”

“…There is some support for this idea, since one of the more robust behavioural effects of destroying the dorsal noradrenergic pathways is an impairment of the learning of new discriminations. This has been demonstrated using both auditory and visual discriminanda in operant conditional discrimination tasks (Everitt et al 1983;Robbins et al 1985;Ho et al 1995) and in some spatial learning tasks (Mason and Lin 1980;Archer 1982;Spyraki et al 1982;Anderson et al 1986;Langlais et al 1993;Compton et al 1995). However, the effects of destroying the dorsal noradrenergic pathway on conventional behavioural indices of memory have been less consistent.…”

Noradrenergic mechanisms in stress and anxiety: I. preclinical studies

“…Lesions of the dorsal noradrenergic bundle, with fibers which project from the locus coeruleus to the cortex, result in an impairment in the acquisition of new information (reviewed in Robbins et al, 1985). Dorsal noradrenergic bundle lesions have been shown to result in an impairment in visual discrimination tasks when a distracting noise is presented immediately before the test, suggesting a specific role of norepinephrine in the attentional component of memory storage (Cole and Robbins, 1992).…”

Effect of destruction of noradrenergic neurones with DSP4 on performance on a free-operant timing schedule

“…It is well known that destruction of the ascending noradrenergic pathways can disrupt positively reinforced operant behaviour in a wide variety of experimental tasks (see Mason 1984;Robbins et al 1985;Bradshaw and Szabadi 1989). Two recent experiments carried out in this laboratory investigated the e¤ects of destroying the noradrenergic input to the neocortex and hippocampus using a selective neurotoxin, DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], on operant timing behaviour.…”