The effects of lesions to ascending noradrenergic neurons on discrimination learning and performance in the rat

Everitt, Barry J.; Robbins, Trevor W.; Gaskin, M.; Fray, P.J.

doi:10.1016/0306-4522(83)90142-2

Cited by 104 publications

(39 citation statements)

References 30 publications

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“…Nevertheless, depletion of brain NE is known to reduce the expression of LTP in the dentate gyrus. Depletion of brain NE also impairs acquisition of learning in spatial discrimination tasks, particularly when auditory or visual cues were involved; administration of NE, however, enhances acquisition of learning (38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine induces pathway-specific long-lasting potentiation and depression in the hippocampal dentate gyrus.

Dahl

Sarvey

1989

Proc. Natl. Acad. Sci. U.S.A.

134

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The study presented here indicates that norepinephrine (NE) selectively induces long-lasting modifications of synaptically mediated responses in the dentate gyms ofthe rat hippocampal slice. A low concentration of NE (1.0 ,AM; in the presence of 50 jcM phentolamine, an a-adrenergic antagonist) or a 1.0 jaM concentration of the specific (3-adrenergic agonist isoproterenol induced long-lasting pathway-specific alterations of granule cell electrophysiological responses. Excitatory postsynaptic potentials and population spikes evoked by stimulation of the medial perforant pathway (PP) were potentiated for more than 45 min. In contrast, responses to lateral PP stimulation were depressed for the same period. Both potentiation and depression were blocked by the (8-adrenergic antagonist propranolol (1.0 jzM). These results indicate that NE can act differentially on projections to the dentate gyrms arising in the entorhinal cortex. Such selective persistent modifications of cortical circuits may be involved in processes in the mammalian brain underlying attention, learning, and memory.Mnemonic processes are thought to be initiated as persistent modifications of neuronal responses (1). The hippocampal formation, a cortical structure reputed to be involved in memory (2), is exemplary in this regard. Long-term potentiation (LTP) of synaptically mediated responses in the hippocampus and dentate gyrms has been induced by high-frequency stimulation of afferents (3) and intrahippocampal pathways (4). A persistent potentiation of dentate gyrus granule cell activation not requiring high-frequency afferent stimulation is seen after exposure to norepinephrine (NE). This effect is known as NE-induced long-lasting potentiation (NELLP) (5).LTP and NELLP in the dentate gyrus are seen as increments in amplitude of granule cell excitatory postsynaptic potentials (EPSPs) and population spikes evoked by stimulation of the perforant pathway (PP). This pathway, the major input to the hippocampus via the dentate gyrus, consists of axons whose cell bodies are located in the lateral and medial entorhinal cortices, respectively (6, 7). Medial and lateral PP terminals differ histochemically, and activation is differentially affected by naloxone and excitatory and inhibitory amino acid ligands (8-10). Although high-frequency stimulation of either the medial or the lateral PPs can produce LTP (11, 12), when LTP is induced in one pathway there is a concurrent long-lasting depression of responses evoked by activation of the other pathway (13).Relationships between NELLP and LTP are not yet well understood, but NE is apparently necessary for a complete expression of LTP in the dentate gyrus (14, 15) and, when paired with high-frequency stimulation, NE may facilitate LTP induction in hippocampal field CA3 (16). Furthermore, D-(-)-2-amino-5-phosphonovaleric acid, an N-methyl-D-aspartate receptor antagonist that blocks LTP in the dentate gyrms (17), also blocks the induction of NELLP (18). In this report, we present results from electrophysiologi...

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Section: Discussionmentioning

confidence: 99%

Norepinephrine induces pathway-specific long-lasting potentiation and depression in the hippocampal dentate gyrus.

Dahl

Sarvey

1989

Proc. Natl. Acad. Sci. U.S.A.

134

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“…For many years, the locus coeruleus (LC)-NE system has been known to influence attention and cognition functioning, participating in the maintenance of states of high arousal and vigilance, and contributing to general processes underlying learning and memory (AstonJones et al, 1999;Berridge and Waterhouse, 2003;Everitt et al, 1983;Foote et al, 1983;Langlais et al, 1993;Rajkowski et al, 1994). For instance, it has been proposed that the regulation of attention by LC-NE neurons has an inverted-U-shaped profile, with either hypo-or hyperactivity of tonic LC-NE discharge rates disrupting the ability to maintain focused attention (Aston-Jones et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Alsene

Carasso²,

Connors

et al. 2006

Neuropsychopharmacol

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Prepulse inhibition (PPI) refers to the attenuation of startle when a weak prestimulus precedes the startling stimulus. PPI is deficient in several psychiatric illnesses involving poor sensorimotor gating. Previous studies indicate that a1 adrenergic receptors regulate PPI, yet the extent to which these effects are mediated by central vs peripheral receptors is unclear. The present studies compared the effects of intracerebroventricular (ICV) vs intraperitoneal (IP) delivery of several a1 receptor agonists on PPI. Male Sprague-Dawley rats received either cirazoline (0, 10, 25, 50 mg/5 ml), methoxamine (0, 30, 100 mg/5 ml), or phenylephrine (0, 3, 10, 30 mg/5 ml) ICV immediately before testing. Separate groups received either cirazoline (0, 0.25, 0.50, 0.75 mg/kg), methoxamine (0, 2, 5, 10 mg/kg), or phenylephrine (0, 0.1, 2.0 mg/kg) IP 5 min before testing. PPI, baseline startle responses, and piloerection, an index of autonomic arousal, were measured. Cirazoline disrupted PPI; effective ICV doses were approximately six times lower than effective IP doses. Methoxamine disrupted PPI after ICV infusion but failed to affect PPI with IP doses that were up to 30-fold higher than the effective ICV dose. Phenylephrine disrupted PPI with ICV administration, but did not alter PPI after IP injection of even a 20-fold higher dose. None of the ICV treatments altered baseline startle magnitude, but phenylephrine and methoxamine lowered startle after administration of high systemic doses. Piloerection was induced by cirazoline via either route of administration, and by IP methoxamine and phenylephrine, but not by ICV infusion of methoxamine or phenylephrine. These findings indicate that a1 receptor-mediated PPI disruption occurs exclusively through stimulation of central receptors and is dissociable from alterations in baseline startle or autonomic effects.

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“…Fifty-nine percent is better than chance performance for 128 trials/session. The data are from an unpublished replication by of earlier results of Everitt et al (1983). errors made on each session backward from the one at which the 85 % criterion was attained). Regression lines are fitted in Figure 2 to the sensibly linear portion of the plots beginning from Session 2; these account for a large proportion of the variance (about 90%) and also differ significantly [F(1,504) = 14.41, P < .01], with the slope for the DNAB group being more shallow.…”

Section: Acquisition Of Appetitive Conditional Discriminationmentioning

confidence: 99%

“…Since the LC, via the DNAB, contributes only about 20% of the hypothalamic NA projection, it seems likely that the 6-0HDA place- (Dooley et al, 1984). Carli et al (1983), and an account of the assay procedure in Everitt et al (1983) Everitt et al, 1983, and ment also damages, to a variable extent, the NA pathways to the hypothalamus arising from NA cell bodies in the medulla. Indeed, it is now clear that a major proportion of Al axons leave the ventral noradrenergic bundle (V NAB) in the caudal midbrain to join the DNAB (Sawchenko & Swanson, 1981), and these will be unavoidably damaged after 6-0HDA lesions of the DNAB, leading to considerable hypothalamic NA loss.…”

Section: Acquisition Of Appetitive Conditional Discriminationmentioning

confidence: 99%

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

et al. 1985

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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-

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The effects of lesions to ascending noradrenergic neurons on discrimination learning and performance in the rat

Cited by 104 publications

References 30 publications

Norepinephrine induces pathway-specific long-lasting potentiation and depression in the hippocampal dentate gyrus.

Norepinephrine induces pathway-specific long-lasting potentiation and depression in the hippocampal dentate gyrus.

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

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

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