Margalida Coll-Andreu

Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise

The effect of long-term voluntary exercise (running wheel) on anxiety-like behaviour (plus maze and open field) and learning and memory processes (object recognition and two-way active avoidance) was examined on Wistar rats. Because major individual differences in running wheel behaviour were observed, the data were analysed considering the exercising animals both as a whole and grouped according to the time spent in the running wheel (low, high, and very-high running). Although some variables related to anxiety-like behaviour seem to reflect an anxiogenic compatible effect, the view of the complete set of variables could be interpreted as an enhancement of defensive and risk assessment behaviours in exercised animals, without major differences depending on the exercise level. Effects on learning and memory processes were dependent on task and level of exercise. Two-way avoidance was not affected either in the acquisition or in the retention session, while the retention of object recognition task was affected. In this latter task, an enhancement in low running subjects and impairment in high and very-high running animals were observed.

Effects of pretraining paradoxical sleep deprivation upon two-way active avoidance

In order to study whether paradoxical sleep (PS) is necessary to prepare subjects for the subsequent learning of a distributed two-way active avoidance conditioning, 10 rats were subjected to 5 h of paradoxical sleep deprivation (PSD group) by means of the platform method immediately before each of 5 acquisition sessions (one daily), as well as before a long-term retention (LTR) session (14 days). Another group of rats (PSD control group; n = 10) were placed on large platforms as a control for the side effects induced by PSD platforms. Rats in the dry control group (n = 10) did not receive any treatment. The number of avoidances of the PSD group was significantly lower on the 1st, 2nd and 3rd acquisition sessions compared to the PSD control group, and on the 2nd and 3rd sessions compared to the dry control group. PSD rats made significantly less intertrial crossings than dry controls on the 2nd and 3rd acquisition sessions, but no significant correlations were found between this variable and the number of avoidances. Therefore, our results are not fully in contradiction with the hypothesis that PS previous to the training sessions might prepare the animal for subsequent learning, although the influence of locomotor changes upon the performance of PSD subjects cannot be fully rejected.

Behavioral evaluation of the stress induced by the platform method for short-term paradoxical sleep deprivation in rats

To evaluate whether the results of short-term PSD (Paradoxical Sleep Deprivation) using the platform method can be influenced by stress, changes in body weight and in behavioral indices (food and water intake and ambulation and defecation in an open field) were measured in rats after each of four 5-hour sessions of confinement to small or large platforms. The animals of the two platform groups when compared to animals kept in home cages showed a similar decrease in body weight which was significant only after the first day of treatment, while no changes in the other measures were observed. It is concluded that 1) the effects of stress induced by short-term confinement to platforms do not seem to be a remarkable confounding factor in short-term PSD studies and 2) large platforms can be used both as an adequate stress control for small platforms and as a means of adapting the animals to the method.

The parafascicular nucleus and two-way active avoidance: effects of electrical stimulation and electrode implantation

Abstract To evaluate whether electrical stimulation of the parafascicular nucleus (PF) can improve short-term (24 h) and/or long-term (21 days) retention of two-way active avoidance, rats were implanted with an electrode at this nucleus (experimental groups) or above it (control groups). After a single 30-trial acquisition session, experimental groups were submitted to a 10-min session of electrical stimulation. Results showed that the simple implantation of an electrode at the posterior PF enhanced by itself the acquisition of two-way active avoidance, in such a way that the subsequent stimulation of this region may have been unable to further improve the performance of the rats. On the other hand, parafascicular stimulation improved the 24-h retention of the task in a site-specific way, since this effect was mainly seen after stimulation of the central PF region. The facilitative effect on 24-h retention could also depend on the level of performance achieved during the acquisition session, because this improvement was only evidenced in poorly learning animals. No effects were found on 21-day retention. The present results confirm the involvement of the PF in learning and memory and the functional heterogeneity of this nucleus.

Impairment of two-way active avoidance after pedunculopontine tegmental nucleus lesions: effects of conditioned stimulus duration.

It was investigated whether the disruptive effects of bilateral lesions of the pedunculopontine tegmental nucleus on two-way active avoidance might vary depending on variations of task demand. The animals were either subjected to bilateral electrolytic lesions of the pedunculopontine tegmental nucleus (Lesion groups) or were sham-operated (Control groups). All the rats were subjected to two 30-trial sessions of two-way active avoidance (separated by ten days), using either a 10-s conditioned stimulus (low task demand) or a 3-s conditioned stimulus (high task demand). The lesions induced a significant disruption of two-way active avoidance in the two conditions tested, but, in both lesioned and control rats, the number of avoidance responses was higher when the 10-s conditioned stimulus was used. In lesioned animals, the condition of high task demand was associated with a significant increase of escape failures. Lesions did not affect locomotor activity during the period of adaptation to the conditioning apparatus, but induced training-specific motor deficits (a decrease of intertrial crossings and an enhancement of escape latencies) regardless of the specific training conditions used. The results are discussed in terms of the influences of the pedunculopontine tegmental nucleus in thalamocortical and striatal systems.

Effects of pedunculopontine tegmental nucleus lesions on emotional reactivity and locomotion in rats.

Bilateral damage to the pedunculopontine tegmental nucleus (PPTg) has been found to impair several learning tasks; however, it is not clear whether this effect could be at least partially attributable to changes in the rat emotional reactivity and/or spontaneous locomotion. Therefore, the present work has tested the effects of bilateral electrolytic lesions of the PPTg on the behaviour of rats in the elevated plus-maze and the open field test. Because the behaviour of rats in learning and emotional tasks can be sensitive to routine experimental manipulations, we also have tested the effects of brief pre-surgical handling procedures on anxiety-like behaviours and locomotion in both lesioned and control rats. Lesions of the pedunculopontine tegmental nucleus (1). did not have any effects on spontaneous locomotor activity and (2). did not increase emotional reactivity. In fact, there was a slight bias towards a reduction in anxiety-like behaviours in lesioned rats, as evidenced by a significant increase in the number of open arm entries. Pre-surgical handling induced a slight decrease of emotional reactivity and a slight increase of exploratory activity. We conclude that damage to the pedunculopontine tegmental nucleus is not accompanied by either an enhancement of emotional reactivity or by an altered spontaneous locomotion.

Facilitation of shuttle-box avoidance by the platform method : temporal effects

Two experiments were carried out in order to 1) replicate a previous finding according to which the treatment on large platforms (commonly used as control for the stress induced by smaller paradoxical sleep deprivation platforms) can facilitate the acquisition and long-term retention (LTR) of a distributed shuttle-box avoidance in rats, and 2) further examine the temporal conditions in which that facilitation can be observed. The results showed that an immediate posttraining treatment lasting 6 hours induced a significant improvement of acquisition both when applied in the light (8 a.m.) and in the dark cycle (8 p.m.), while the LTR (10 and 31 days) seemed to be better preserved when the treatment was applied during the dark cycle. A shorter treatment (3 h) had no effect upon shuttle-box avoidance, regardless of whether it was applied in the dark or in the light cycle and whether it was immediate or delayed for 3 h. In summary, under certain temporal conditions, a posttraining immediate treatment on large platforms can facilitate the acquisition and/or the LTR of shuttle-box avoidance. Stress hormones and/or the enhancement of CNS arousal are suggested to be some of the mechanisms operating in this facilitatory effect.

Facilitatory effects of thalamic reticular nucleus lesions on two-way active avoidance in rats

Abstract Two experiments were performed in order to study the effects of lesions of the rostral thalamic reticular nucleus (Rt) on two-way active avoidance. Male wistar rats were subjected to either a bilateral electrolytical lesion of the rostral Rt or to control procedures. After recovery, all rats were trained in either a distributed (five training sessions, ten trials each; experiment I) or a massed (a single 30-trials session; experiment II) two-way, active-avoidance task. The level of long-term retention of the task was assessed 10 days later. Lesioned rats showed an overall higher performance than control rats both in experiment I (with lesions affecting the rostral Rt and small portions of some adjacent nuclei) and in experiment II (with lesions almost restricted to the rostral Rt). In contrast, detrimental effects on other tasks have been reported in the literature. Although it cannot be ruled out that those differences might be due to methodological factors, they also might be indicative of an action of rostral Rt lesions on certain mechanisms (either indirectly or directly related to information processing) that could be differentially required depending on the kind of learning task. The latter possibility is discussed in terms of the role played by this nucleus as a modulator of thalamocortical transmission, attentional mechanisms and cortical arousal.

Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: time- and site-specific effects on two-way active avoidance conditioning.

The pedunculopontine tegmental nucleus (PPTg) is involved in the regulation of thalamocortical transmission and of several functions related to ventral and dorsal striatal circuits. Stimulation of the PPTg in anesthetized animals increases cortical arousal, cortical acetylcholine release, bursting activity of mesopontine dopaminergic cells, and striatal dopamine release. It was hypothetized that PPTg stimulation could improve learning by enhancing cortical arousal and optimizing the activity of striatal circuits. We tested whether electrical stimulation (ES) of the PPTg, applied to freely-moving awake rats previously implanted with a chronic electrode, would improve the acquisition and/or the retention of two-way active avoidance conditioning, and whether this effect would depend on the specific PPTg region stimulated (anterior vs posterior) and on the time of ES: just before (pre-training) or after (post-training) each of three training sessions. The treatment consisted of 20 min of ES (0.2 ms pulses at 100 Hz; current intensity: 40-80 microA). The results showed that (1) this stimulation did not induce either any signs of distress nor abnormal behaviors, apart from some motor stereotyped behaviors that disappeared when current intensity was lowered; (2) pre-training ES applied to the anterior PPTg improved the acquisition of two-way active avoidance, (3) no learning improvement was found after either post-training ES of the anterior PPTg, or pre- and post-training ES of the posterior PPTg. The results give support to a role of PPTg in learning-related processes, and point to the existence of functional PPTg regions.

Traumatic brain injury in late adolescent rats: effects on adulthood memory and anxiety.

The consequences of traumatic brain injury (TBI) sustained during late adolescence (7 weeks old) on spontaneous object recognition memory and on anxiety-like behaviors in the elevated plus maze were tested in rats during adulthood. Testing took place at 2 different postinjury times, in separate groups: 3 and 6 weeks, when animals were 10 and 13 weeks old, respectively. The rats were either submitted to controlled cortical impact injury, an experimental model of focal TBI with contusion, or were sham-operated. TBI animals failed to remember the familiar object and had a significantly lower performance than sham-operated animals, indicating memory disruption, when the retention delay was 24 hr, but not when it was 3 hr. TBI did not have any significant effect on the main anxiety-related behaviors, but it reduced time in the central platform of the elevated plus maze. The effects of TBI on memory and on anxiety-like behaviors were similar at the 2 postinjury times. In both TBI and sham-operated groups, animals tested 6 weeks after surgery had lower anxiety-related indices than those tested at 3 weeks, an effect that might be indicative of reduced anxiety levels with increasing age. In summary, focal TBI with contusion sustained during late adolescence led to object recognition memory deficits in a 24-hr test during adulthood but did not have a major impact on anxiety-like behaviors. Memory deficits persisted for at least 6 weeks after injury, indicating that spontaneous modifications of these functional disturbances did not take place along this time span.