A comparison of intradimensional and extradimensional shift learning in pigeons

In each of three experiments pigeons were trained on a simultaneous discrimination between stimuli that differed in both colour and orientation. For half the birds the colour dimension was relevant and for half orientation was relevant (i.e., differences along that dimension were correlated with reward and nonreward). All birds were then shifted to a second discrimination between new colours and orientations. For half this constituted an intradimensional shift in that the previously relevant dimension remained relevant; for the remainder the previously irrelevant dimension was made relevant (an extradimensional shift). Contrary to the predictions of attentional theory, the two types of shift were learned with equal ease.     

A new perceptual bias reveals suboptimal population decoding of sensory responses

Several studies have reported optimal population decoding of sensory responses in two-alternative visual discrimination tasks. Such decoding involves integrating noisy neural responses into a more reliable representation of the likelihood that the stimuli under consideration evoked the observed responses. Importantly, an ideal observer must be able to evaluate likelihood with high precision and only consider the likelihood of the two relevant stimuli involved in the discrimination task. We report a new perceptual bias suggesting that observers read out the likelihood representation with remarkably low precision when discriminating grating spatial frequencies. Using spectrally filtered noise, we induced an asymmetry in the likelihood function of spatial frequency. This manipulation mainly affects the likelihood of spatial frequencies that are irrelevant to the task at hand. Nevertheless, we find a significant shift in perceived grating frequency, indicating that observers evaluate likelihoods of a broad range of irrelevant frequencies and discard prior knowledge of stimulus alternatives when performing two-alternative discrimination.     

Short-term incidental memory for irrelevant cues

A new analysis of previously published studies of delayed matching-to-sample (DMTS) water-escape and the results of a new food-reinforced discrimination study are presented. In both cases, male Sprague-Dawley rats demonstrated short-term incidental memory for irrelevant cues in the context of two-alternative forced-choice problems that required learning about relevant cues. In the DMTS experiments, relevant and irrelevant cues were place or brightness. In the discrimination experiment, the relevant cues were place, brightness or a visual-tactile maze insert. In all experiments, after the rats attained high-level performance, consistently making choices with respect to the relevant stimuli, response latencies to the correct relevant cue were shorter when the irrelevant cue value(s) was the same as on the immediately preceding trial. These latency differences are interpreted as indicating that the rats demonstrated short-term incidental memory for the irrelevant cues. This mnemonic phenomenon resembles priming, an implicit form of memory.     

Prevention of hypertension in the SH rat: effects of differential central catecholamine depletion.

Six-hydroxydopamine (6-OHDA) was administered intraventricularly to 6-week-old male spontaneously hypertensive (SH) rats of the Okomoto strain and to normotensive rats of the Kyoto-Wistar strain. In addition, bilateral lateral tegmental lesions were placed in 35-40-day-old SH rats to interrupt ascending noradrenergic pathways. SH rats treated with 6-OHDA did not develop hypertension and had lower heart rates than control rats. Blood pressure and heart rate of Kyoto-Wistar animals were unaffected by the drug treatment. 6-OHDA produced widespread depletion of norepinephrine throughout the CNS of both SH and Kyoto-Wistar rats. Bilateral lateral tegmental lesions interrupted the dorsal noradrenergic bundle and depleted forebrain norepinephrine. These lesions did not prevent the development of hypertension and led to an increased heart rate. It is concluded that 6-OHDA does not produce its effect through a nonspecific lowering of blood pressure, but rather, that it interferes with the expression of the hypertensive syndrome. The lack of effect seen following depletion of forebrain norepinephrine as the result of interruption of the dorsal noradrenergic bundle indicates that the fibers destroyed by this lesion are not essential for the development of genetically determined hypertension.     

Dorsal noradrenergic bundle lesions fail to alter opiate withdrawal or suppression of opiate withdrawal by clonidine

Previous work has shown that clonidine effectively supresses many of the signs of opiate withdrawal. The present study was designed to test the hypothesis that the supression of opiate withdrawal by clonidine is mediated by forebrain noradrenergic projections of the locus coeruleus. Two groups of 24 rats each were subjected to either a 6-hydroxydopamine lesion of the dorsal noradrenergic bundle (Lesion group) or a sham, vehicle injection (Sham group). All rats were made dependent on morphine by subcutaneous implantation of one 75 mg silastic morphine pellet for three days followed by 3 more days with two additional 75 mg pellets. Following removal of the morphine pellet, withdrawal was precipitated in all rats by subcutaneous injection of 4 mg/kg of naloxone. Pretreatment 10 min. before withdrawal with clonidine (0.1 or 0.2 mg/kg) produced a significant attenuation of withdrawal signs as compared to saline injected rats; this effect was equally significant in both sham and lesion groups. Lesions of the locus coeruleus had no effect on withdrawal, nor did they affect the ameliorating action of clonidine. These results substantiate the observation that clonidine can effectively attenuate signs of opiate withdrawal in the rat, but fail to support the hypothesis that these effects are mediated by the forebrain projections of the locus coeruleus.     

Brain (Na+, K+)-ATPase and Noradrenergic Activity: Effects of Hyperinnervation and Denervation on High-Affinity Ouabain Binding

Abstract: To examine the role of nerve-specific (Na⁺, K⁺)-ATPase in chronic changes in noradrenergic activity, we examined the effects of noradrenergic denervation and hyperinnervation on p -nitrophenylphosphatase activity and on total and nerve-specific ouabain binding. High-affinity and erythrosin B-sensitive binding were compared as measurements of nerve-specific binding. Hyperinnervation and denervation was produced in cerebellum and cerebral cortex, respectively, by 6-hydroxydopamine lesions of the dorsal noradrenergic bundle. Hyperinnervation increased, and denervation decreased, enzyme activity, high-affinity ouabain inhibition, and erythrosin B-sensitive ouabain binding. As (Nat⁺, K⁺)-ATPase has a major role in the regulation of neural excitability and energy metabolism, and the ouabain binding site has been shown to have endogenous ligands, these changes in (Na⁺, K⁺)-ATPase may be important in the long-term regulation of neuron function by norepinephrine.     

Dissociate destruction of noradrenaline and dopamine descending projections in the thoracic spinal cord of the rat

Intracisternal administration of 6-hydroxydopamine to male Wistar rats produced a near complete depletion of noradrenaline levels, as measured by a radioenzymatic assay in micropunches sampled from the dorsal, lateral and ventral horns of the thoracic spinal cord. This drastic effect was reversed by pretreatment with desipramine, a pharmacological inhibitor of noradrenergic neuron uptake. Surprisingly, dopamine content was not significantly reduced. The question as to whether such a lack of concomitant dopamine decrease might be inherent to the dopamine assay itself could be answered by the results obtained with both pharmacological (reserpine) treatments and interference determinations in the dopamine assay. The relative potency of 6-hydroxydopamine to destroy noradrenergic and dopaminergic neurons might account for their differential behavior. Conversely, a large midbrain section performed by knife cut could decrease both dopamine and DOPAC (one of its major acid metabolites) in the thoracic lateral horn and partly in the ventral one. The noradrenaline content was not reduced. Results are discussed in light of recently reported data on dopaminergic descending projections to the spinal cord. The lesion procedures presented here seem to provide valuable tools to dissociate noradrenergic from dopaminergic spinal projections, which is necessary for further anatomical and functional studies on these systems.     

Lesions of the ventral noradrenergic bundle prevent the rise in blood pressure induced by social deprivation stress in the rat

1. Hypertension can be induced by some types of stress in the rat. The aim of the present work was to study the putative implication of brain norepinephrine (NE) in blood pressure increase due to social deprivation stress. 2. The effects of 6-hydroxydopamine (6-OHDA) lesions of the ventral noradrenergic bundle (VNEB) on the hypertensive response induced by brief social deprivation stress in young Wistar rats were examined. NE, dopamine (DA), and epinephrine (EPI) levels were measured by HPLC coupled with electrochemical detection in two brain areas (hypothalamus and medulla oblongata) relevant for blood pressure regulation. 3. VNEB lesions prevented the hypertensive response produced by isolation. Twelve or 20 days after 6-OHDA administration, NE and EPI but not DA levels decreased in the hypothalamus of the lesioned rats. In contrast, no catecholamine changes were detected in medulla oblongata. 4. These data suggest that the VNEB plays a role in the triggering of the hypertensive response induced by social deprivation stress in young Wistar rats.     

Subacute Noradrenergic Agonist Infusions In Vivo Increase Na+, K+-ATPase and Ouabain Binding in Rat Cerebral Cortex

In order to investigate the specificity of noradrenergic effects on Na+, K+-ATPase, we infused noradrenergic agonists into the cerebral ventricles of rats, with or without depletion of forebrain norepinephrine. Infusion of norepinephrine, isoproterenol, or phenylephrine increased ouabain binding in intact rats, whereas clonidine infusion decreased binding. Depletion of forebrain norepinephrine by destruction of the dorsal noradrenergic bundle reduced ouabain binding. Norepinephrine infusion reversed the effect of dorsal bundle lesion; isoproterenol and phenylephrine increased ouabain binding in lesioned rats, but did not restore the effect of the lesions. Clonidine had no effect in lesioned rats. Effects on Na+, K+-ATPase activity were similar, but smaller. These results suggest that stimulation of both alpha 1- and beta-noradrenergic receptors may be necessary for optimal Na+, K+-ATPase, and that clonidine reduces Na+, K+-ATPase indirectly through decreased norepinephrine release.     

Disruption of latent inhibition in ISIAH rats with stress-sensitive arterial hypertension

Latent inhibition phenomenon is used in the study of processes of selective attention in the context reinforcing training. The purpose of this study was a comparative analysis of the ability to ignore irrelevant stimuli in hypertensive ISIAH rats and normotensive Wistar rats with different psychoemotional statuses. Latent inhibition was formed in the passive and active avoidance tasks the development of which was preceded by repeated presentation (pre-exposition) conditioned stimulus without reinforcement. In ISIAH rats, disruption of latent inhibition in both behavioural tasks was observed as compared with Wistar rats. These data suggest that the deficit of selection information in ISIAH rats is caused by congenital weakness of internal inhibition in the adaptation to anxiogenic stimuli.     

Lateral sensitivity modulation explains the flanker effect in contrast discrimination

We used a dual-masking paradigm to study how contrast discrimination can be influenced by the presence of adjacent stimuli. The task of the observer was to detect a target superimposed on a pedestal in the presence of flankers. The flankers (i) reduce the target threshold at zero pedestal contrast, (ii) shift the target threshold versus pedestal contrast (TvC) function horizontally to the left on a log-log plot at high pedestal contrasts, and (iii) reduce the size of pedestal facilitation at low pedestal contrasts. The horizontal shift at high pedestal contrasts suggests that the flanker effect is a multiplicative factor that cannot be explained by previous models of contrast discrimination. We extend the divisive inhibition model of contrast discrimination by implementing the flanker effect as a lateral multiplicative sensitivity modulation. This extended model provides a good account of the data.     

Human implicit memory for irrelevant dimension values is similar to rats' incidental memory in simultaneous discrimination tasks

Participants completed a category-learning task in which they needed to discover which of three stimulus dimensions (shape, color or size) was relevant. After meeting a learning criterion (nine of 10 consecutive correct responses), participants continued making categorization choices and response latencies associated with these trials were examined. In both Experiments 1 and 2, people responded reliably faster when correct responses matched the previous responses with respect to irrelevant dimension values. Thus, they demonstrated a form of incidental short-term memory analogous to that we previously reported in studies of rats. In Experiment 2, participants' explicit memory for irrelevant dimension values was assessed after category learning was complete. The results indicated that people were unaware of the irrelevant dimension values encountered on trials preceding surprise probe trials. This indicates that memory for the irrelevant dimension values was implicit (i.e. unconscious). The findings are discussed with respect to both human and non-human studies of hippocampus-independent memory and implicit memory.     

CHANGES IN CENTRAL NORADRENALINE NEURONSADMINISTRATION AFTER SYSTEMIC 6-HYDROXYDOPAMINE ADMINISTRATION

—Intravenous injection of a large dose of 6-hydroxydopamine (100 mg/kg) to adult rats caused a significant and long-lasting reduction (about 30 per cent) of the in oirro uptake of [³H]NA in the cerebral cortex and spinal cord, while no changes were seen in the hypothalamus. The endogenous NA in whole brain was similarly reduced (about 20 per cent). Fluorescence histochemistry revealed catecholamine accumulations which are degenerative signs, induced by 6-hydroxydopamine, in axons of the dorsal NA bundle innervating the cerebral cortex. It is concluded that the blood–brain barrier in adult rats is not completely protective with respect to the neurotoxic action of systemically injected 6-hydroxydopamine, which can produce degeneration of a significant number of NA nerve terminals in the cerebral cortex and spinal cord. Previous studies have shown that 6-hydroxydopamine caused a permanent and selective degeneration of a large number of central NA nerve terminals when injected systemically up to 1 week after birth, due to an incompletely developed blood-brain barrier. This barrier for 6-hydroxydopamine develops between the 7th and 9th day after birth (Sachs , 1973). In the present study 6-hydroxydopamine was found to cause a small transient reduction in [³H]NA uptake in cerebral cortex of rats between 9 and 28 days of age, while in older rats the damage produced by 6-hydroxydopamine was long-lasting. Thus, the NA nerves ascending to the cerebral cortex seem to possess a regenerative capacity to a 6-hydroxydopamine-induced degeneration up to about 28 days postnatally, but which later disappears or is markedly retarded.     

Functional role of the dorsal and ventral hippocampus in defensive behavior in the rat

Bilateral electrolytic lesions of the dorsal hippocampus of white rats were shown to facilitate elaboration of a conditioned response of active avoidance of pain shock in a shuttle-box. The lesions of the ventral hippocampus had no effect on conditioning. The ventral hippocampal lesions led to a complete failure to form differential inhibition. In rats with the dorsal hippocampal lesions an acquisition of partial (up to 60 per cent) discrimination of stimuli was possible. The differences in avoidance conditioning and elaboration of differential inhibition in rats with the dorsal and ventral hippocampal lesions are supposed to be caused by the changes of general excitability and emotional state of animals as well as by a specific role of the ventral hippocampus in memory consolidation.     

Effects of phencyclidine on schedule-controlled responding following neurotoxic lesions of the striatum

The effects of phencyclidine on an operant task were evaluated prior to and after neurotoxic lesions of the striatum in rats. Subjects were trained to respond on a fixed-interval 90-second schedule for water presentation. The degree to which phencyclidine disrupted responding was first evaluated (dose range 1.0-4.0 mg/kg). The subjects were then divided into three matched groups and received bilateral intraventricular injections of 6-hydroxydopamine (6-OHDA) (100 microg), kainic acid (0.25 microg), or vehicle delivered stereotaxically. 6-OHDA was used to destroy the presynaptic neurons of the nigro-striatal pathway and kainic acid was employed to destroy the postsynaptic neurons whose cell bodies are located in the striatum. Following recovery, the phencyclidine dose-response curve was repeated in the fixed-interval paradigm. It was observed that 6-OHDA-induced damage resulted in a rightward shift of the dose-response curve indicating tolerance to phencyclidine and caused a significant depletion of striatal dopamine and gamma-aminobutyric acid (GABA). Kainic acid-induced damage resulted in a leftward shift in the dose-response curve indicating sensitivity to the schedule-disruptive effects of phencyclidine and produced a significant GABA depletion. The vehicle-treated rats exhibited no shift in their sensitivity to phencyclidine. These observations indicate that the effects of phencyclidine are mediated, at least in part, by striatal dopaminergic neurons.     

Shift of the catecholamine levels at stimulation of the hypothalamic emotiogenic zones

Using models of electrical self-stimulation of the positive emotiogenic zones and stimulation of the negative emotiogenic zones of the hypothalamus in rats, we demonstrated that both these stimulations increase the noradrenaline level in the frontal cortex. This shows a nonspecific nature of activation of the dorsal noradrenergic bundle, resulting from motivational excitation. When the frequency of self-stimulation reaction remained stable, activation of the dorsal noradrenergic bundle was moderate, and at decay of the above reaction it returned to the control level. Behavior connected with activation of the motor functions was characterized by an increase in the dopamine and noradrenaline levels in the caudate nucleus. In theglobus pallidum, the dopamine content changed only under conditions of stimulation of the negative emotiogenic zones: these were an increase in the reaction of active avoidance and a decrease in passive avoidance.     

Role of the Central Adrenergic System in the Regulation of Prostaglandin Biosynthesis in Rat Brain

The role of endogenous catecholamines in the regulation of brain prostaglandin (PG) synthesis was studied in the rat. Male rats were injected in the brain lateral ventricle or in the ventral noradrenergic bundle with either the catecholaminergic neurotoxin 6-hydroxydopamine or vehicle. Other groups of rats were injected intraperitoneally with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, or with the inhibitor of dopamine-beta-hydroxylase, FLA-63. All these drugs produced a significant depletion of norepinephrine (NE) content in the cortex and hypothalamus. The rats that had lower levels of NE exhibited reduced capacity to synthesize PGE2 but not thromboxane B2 and 6-keto-PGE1 alpha in the cortex and hypothalamus. However, induced production of PG, stimulated by the bacterial endotoxin lipopolysaccharide (LPS), remained unchanged, namely, a similar (2- to 2.5-fold) increase of PG synthesis was noted in control and in NE-depleted rats. We suggest that the regulation of PG synthesis under basal condition requires intact adrenergic input, whereas LPS-induced production of PG is independent of the adrenergic innervation.     

Brain mechanism of selective listening reflected by event-related potentials

Stimulus selection during selective listening on the basis of simple physical stimulus features is reflected by an event-related potential (ERP) component called the processing negativity (PN). PN has been proposed to indicate a matching or comparison process between the physical features of the stimulus and an ‘attentional trace’, an actively formed and maintained temporary neuronal representation of the features defining the relevant stimuli. According to this theory, the smaller is the difference between the eliciting stimulus and that represented by the attentional trace, the longer time is the stimulus processed, and thus the larger in amplitude and longer in duration is the PN elicited. The relevant stimuli, perfectly matching with the attentional trace, and therefore eliciting the largest and longest-duration PN, are selected for further processing. In the present study, the relevant and irrelevant stimuli differed in pitch, and the magnitude of this pitch separation was varied between different stimulus blocks. The results support the afore-mentioned matching or comparison hypothesis of selective attention by showing that PN is not elicited only by the relevant stimuli but even by irrelevant stimuli, and further that the latter PN is larger in amplitude and longer in duration the more similar the irrelevant stimuli are to the relevant stimuli. This PN, however, was smaller than that to the relevant stimuli even for very small separations, reflecting high accuracy of the discrimination function of the attentional trace mechanism proposed to underly selective listening. The termination of the PN to the irrelevant stimuli was followed by a positivity which thus partly explained the difference (Nd) between the ERPs to the relevant and irrelevant stimuli.     

Distribution of subgroups of neuropeptide Y-immunoreactive and noradrenergic nerves in the female rat uterine cervix

Summary Nerves in the uterine cervix of the rat were examined with regard to co-existence of markers for noradrenaline and neuropeptide Y, and differential tissue innervation by nerves containing different combinations of these markers. Immunohistochemical labeling of single and adjacent serial cryostat sections, and double labeling was employed. Some animals were treated with the noradrenergic neurotoxin, 6-hydroxydopamine. In control animals neuropeptide Y-immunoreactive fibers were numerous in the myometrium and around arteries; noradrenergic fibers were few in the myometrium and moderate in number around arteries. Myometrial neuropeptide Y-immunoreactive fibers were not decreased, but apparently increased, in 6-hydroxydopamine-treated rats; in contrast, perivascular neuropeptide Y-immunoreactive fibers were markedly reduced, but not totally absent. Noradrenergic fibers were absent in the myometrium and around arteries following 6-hydroxydopamine treatment. Labeling of adjacent sections and double labeling revealed coincident labeling of markers for neuropeptide Y and noradrenaline in perivascular, but not myometrial, nerves. We concluded that most myometrial neuropeptide Y-immunoreactive nerves did not contain noradrenaline since they were not sensitive to 6-hydroxydopamine and did not stain doubly; however, perivascular neuropeptide Y-immunoreactive fibers which degenerated after 6-hydroxydopamine treatment and did label doubly must co-store noradrenaline. Some neuropeptide Y-immunoreactive perivascular fibers may contain neuropeptide Y but not noradrenaline. Thus, it appears there is a differential innervation of tissues in the cervix by neuropeptide Y/noradrenergic nerves; this could reflect a differential regulation of tissues innervated by these nerves.     

Evidence that Extracellular Concentrations of Dopamine Are Regulated by Noradrenergic Neurons in the Frontal Cortex of Rats

Abstract: Experiments were performed to confirm that noradrenergic terminals regulate extracellular concentrations of dopamine (DA) in the frontal cortex of rats. The effects of 20 mg/kg 1-[2-[bis(4-fluorphenyl)methoxy]-ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909), a selective inhibitor of DA uptake, and 2.5 mg/kg desipramine (DMI) on the extracellular concentrations of DA in the frontal cortex and striatum were studied in rats given 6-hydroxydopamine (6 µg/µl) bilaterally into the locus coeruleus to destroy noradrenergic terminals. GBR 12909 increased dialysate DA similarly in the striatum of vehicle and 6-hydroxydopamine-treated rats, whereas in the frontal cortex it raised DA concentrations only in lesioned animals. DMI raised extracellular DA concentrations in the frontal cortex but not in the striatum of controls. The effect of DMI on cortical DA was abolished by the 6-hydroxydopamine lesion. GBR 12909, at a subcutaneous dose of 20 mg/kg, further increased cortical dialysate DA in rats given DMI intraperitoneally at 20 mg/kg or through the probe at 10⁻⁵ mol/L. The data support the hypothesis of an important regulation of the extracellular concentrations of DA in the frontal cortex by noradrenergic terminals.