Papers by Pilar Segura-torres
Increase in c-Fos and Arc protein in retrosplenial cortex after memory-improving lateral hypothalamic electrical stimulation treatment
Neurobiology of Learning and Memory, 2016
Post-training Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH), a kind of re... more Post-training Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH), a kind of rewarding deep-brain stimulation, potentiates learning and memory and increases c-Fos protein expression in specific memory-related brain regions. In a previous study, Aldavert-Vera et al. (2013) reported that post-acquisition LH-ICSS improved 48 h retention of a delay two-way active avoidance conditioning (TWAA) and induced c-Fos expression increase in CA3 at 90 min after administration. Nevertheless, this c-Fos induction was only observed after the acquisition session and not after the retention test at 48 h, when the ICSS improving effect was observed on memory. This current study aims to examine the hypothesis that post-training ICSS treatment may stimulate c-Fos expression at the time of the TWAA retention test in retrosplenial cortex (RSC), a hippocampus-related brain region more closely related with long-lasting memory storage. Effects of ICSS on Arc protein, a marker of memory-associated synaptic plasticity, were also measured by immunohistochemistry in granular and agranular RSC. The most innovative results are that the ICSS treatment potentiates the c-Fos induction across TWAA conditions (no conditioning, acquisition and retention), specifically in layer V of the granular RSC, along with increases of Arc protein levels in the granular but not in agranular areas of RSC ipsilaterally few hours after ICSS. This leads us to suggest that plasticity-related protein activation in the granular RSC could be involved in the positive modulatory effects of ICSS on TWAA memory consolidation, opening a new approach for future research in ICSS memory facilitation.
Rewarding brain stimulation reverses the disruptive effect of amygdala damage on emotional learning
Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulatio... more Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulation, is able to improve acquisition and retention of implicit and explicit memory tasks in rats. SS treatment is also able to reverse cognitive deficits associated with aging or with experimental brain injuries and evaluated in a two-way active avoidance (2wAA) task. The main objective of the present study was to explore the potential of the SS treatment to reverse the complete learning and memory impairment caused by bilateral lesion in the lateral amygdala (LA). The effects of post-training SS, administered after each acquisition session, were evaluated on distributed 2wAA acquisition and 10-day retention in rats with electrolytic bilateral LA lesions. SS effect in acetylcholinestaresase (AchE) activity was evaluated by immunohistochemistry in LA-preserved and Central nuclei (Ce) of the amygdala of LA-damaged rats. Results showed that LA lesion over 40% completely impeded 2wAA acquisition and retention. Post-training SS in the LA-lesioned rats improved conditioning and retention compared with both the lesioned but non-SS treated and the non-lesioned control rats. SS treatment also seemed to induce a decrease in AchE activity in the LA-preserved area of the lesioned rats, but no effects were observed in the Ce. This empirical evidence supports the idea that self-administered rewarding stimulation is able to completely counteract the 2wAA acquisition and retention deficits induced by LA lesion. Cholinergic mechanisms in preserved LA and the contribution of other brain memory-related areas activated by SS could mediate the compensatory effect observed.
Neuroscience, 2008
Learning and memory improvement by post-training intracranial self-stimulation has been observed ... more Learning and memory improvement by post-training intracranial self-stimulation has been observed mostly in implicit tasks, such as active avoidance, which are acquired with multiple trials and originate rigid behavioral responses, in rats. Here we wanted to know whether post-training self-stimulation is also able to facilitate a spatial task which requires a flexible behavioral response in the Morris water maze. Three experiments were run with Wistar rats. In each of them subjects were given at least five acquisition sessions, one daily, consisting of 2-min trials. Starting from a random variable position, rats had to swim in a pool until they located a hidden platform with a cue located on its opposite site. Each daily session was followed by an immediate treatment of intracranial self-stimulation. Control subjects did not receive the self-stimulation treatment but were instead placed in the self-stimulation box for 45 min after each training session. In the three successive experiments, independent groups of rats were given five, three and one trial per session, respectively. Temporal latencies and trajectories to locate the platform were measured for each subject. Three days after the last acquisition session, the animals were placed again in the pool for 60 s but without the platform and the time spent in each quadrant and the swim trajectories were registered for each subject. A strong and consistent improvement of performance was observed in the self-stimulated rats when they were given only one trial per session, i.e. when learning was more difficult. These findings agree with our previous data showing the capacity of post-training self-stimulation to improve memory especially in rats with little training or low conditioning levels, and clearly prove that post-training self-stimulation can also improve spatial learning and memory.
Intracranial self-stimulation recovers learning and memory capacity in basolateral amygdala-damaged rats
Neurobiology of Learning and Memory, 2010
We studied the capacity of post-training intracranial self-stimulation (SS) to reverse or amelior... more We studied the capacity of post-training intracranial self-stimulation (SS) to reverse or ameliorate learning and memory impairments caused by amygdala damage in rats. A first experiment showed that lesions of the basolateral amygdala (BLA) slow down acquisition of two-way active avoidance conditioning (2wAA). In a second experiment we observed that a post-training SS treatment administered immediately after each 2wAA conditioning session is able to completely reverse the disruptive effects of the BLA lesions, and the facilitative effect lasts for 10days. A third experiment allowed us to differentiate the strong recuperative effects of the SS treatment from the slight effect caused by overtraining the same conditioning response. We concluded that SS is able to counteract the behavioral deficit induced by BLA damage, probably by activating alternative undamaged brain structures related to learning and memory, such as the hippocampus.
Neurobiology of Learning and Memory, 2008
Post-training intracranial electrical self-stimulation can improve learning and memory consolidat... more Post-training intracranial electrical self-stimulation can improve learning and memory consolidation in rats. However, the molecular mechanisms involved are not known yet. Since previous paradigms of this kind of facilitation are relatively unsuitable to try a molecular approach, here we develop a single and short model of learning and memory facilitation by post-training self-stimulation that could make easier the research of its neural and molecular basis. Thus, three consecutive experiments were carried out to ascertain whether post-training self-stimulation is able to facilitate memory when learning consists of only a brief (5 trials) two-way active avoidance conditioning session. The results of Experiment 1 showed that it is actually possible, and that 48 h after the acquisition session is a very good time to observe the memory improvement. As a way to probe the retroactive effect of self-stimulation, in Experiment 2 we observed that the same self-stimulation treatment given to the subjects not post-training but 48 h before a single two-way active avoidance session does not improve the acquisition of conditioning. In Experiment 3, we showed that the SS facilitative effect observed 48 h after the acquisition session in Experiment 1 was still maintained one week later. We concluded that post-training intracranial self-stimulation can consistently improve memory consolidation even when little acquisition training is given to the animals in a single training session.
Neurobiology of Learning and Memory, 1997
Neurobiology of Learning and Memory, 1995
Intracranial self stimulation upregulates the expression of synaptic plasticity related genes and Arc protein expression in rat hippocampus
Genes, Brain and Behavior, 2013
Post-training lateral hypothalamus (LH) intracranial self stimulation (ICSS) has a reliable enhan... more Post-training lateral hypothalamus (LH) intracranial self stimulation (ICSS) has a reliable enhancing effect on explicit memory formation evaluated in hippocampus-dependent tasks such as the Morris water maze. In this study, the effects of ICSS on gene expression in the hippocampus are examined 4.5 h post treatment by using oligonucleotide microarray and real-time PCR, and by measuring Arc protein levels in the different layers of hippocampal subfields through immunofluorescence. The microarray data analysis resulted in 65 significantly regulated genes in rat ICSS hippocampi compared to sham, including cAMP-mediated signaling as one of the most significantly enriched Database for Annotation, Visualization and Integrated Discovery (DAVID) functional categories. In particular, expression of CREB-dependent synaptic plasticity related genes (c-Fos, Arc, Bdnf, Ptgs-2 and Crem and Icer) was regulated in a time-dependent manner following treatment administration. Immunofluorescence results showed that ICSS treatment induced a significant increase in Arc protein expression in CA1 and DG hippocampal subfields. This empirical evidence supports our hypothesis that the effect of ICSS on improved or restored memory functions might be mediated by increased hippocampal expression of activity-dependent synaptic plasticity related genes, including Arc protein expression, as neural mechanisms related to memory consolidation.
Genes, Brain and Behavior, 2011
Intracranial self-stimulation (ICSS) in the lateral hypothalamus improves memory when administere... more Intracranial self-stimulation (ICSS) in the lateral hypothalamus improves memory when administered immediately after a training session. In our laboratory, ICSS has been shown as a very reliable way to increase two-way active avoidance (TWAA) conditioning, an amygdaladependent task. The aim of this work was to study, in the rat amygdala, anatomical and molecular aspects of ICSS, using the same parameters facilitating TWAA. First, we examined the activation of ipsilateral and contralateral lateral (LA) and basolateral (BLA) amygdala, the main amygdalar regions involved in the TWAA, by the immunohistochemical determination of c-Fos protein expression. Second, we tested the effects of the ICSS treatment on the expression of 14 genes related to learning and memory processes using real-time polymerase chain reaction. Results showed a bilateral increase in c-Fos protein expression in LA and BLA nuclei after ICSS treatment. We also found that Fos, brain-derived nerve growth factor (BDNF ), Arc, inducible cAMP early repressor (ICER), COX-2, Dnajb1, FKpb5 and Ret genes were upregulated in the amygdala 90 min and 4.5 h post ICSS. From this set of genes, BDNF, Arc and ICER are functionally associated with the cAMP-responsive element-mediated gene transcription molecular pathway that plays a pivotal role in memory, whereas Dnajb1 and Ret are associated with protein folding required for plasticity or neuroprotection. Our results suggest that ICSS induces expression of genes related with synaptic plasticity and protein folding functions in the rat amygdaloid area, which may be involved in the molecular mechanisms by which ICSS may improve or restore memory functions related to this brain structure.
Brain Research Bulletin, 2007
To assess whether intracranial self-stimulation (SS) given after memory reactivation could improv... more To assess whether intracranial self-stimulation (SS) given after memory reactivation could improve memory retrieval, we tested the immediate (Experiment 1) and late (24 h; Experiment 2) effects of an SS treatment on the retrieval of a two-way active avoidance conditioning in Wistar rats. Memory was reactivated 24 h after training and the reminder (Rm) used consisted of a 3 s exposure to the conditioned stimulus (a tone) in the same context as in the original learning. SS treatment (2500 trains at 100% of each rat's optimal intensity) was administered immediately afterwards. No significant differences between SS-treated and control groups were observed when the retrieval was tested immediately after the SS treatment with or without memory reactivation. However, retrieval was improved when tested 24 h after SS treatment alone or after the reminder exposure alone. The greatest improvement in avoidance was observed when both treatments were given together, that is, when the SS treatment was administered immediately after memory reactivation. Moreover, there were no significant statistical interactions between the effect of SS treatment and the ones of memory reactivation in any of both experiments. The present results show that the effect of an immediate SS treatment can be added to the ones of memory reactivation causing a strong long-term facilitation of memory retrieval.
Intracranial self-stimulation in the parafascicular nucleus of the rat
Brain Research Bulletin, 1999
A behavioral analysis of intracranial self-stimulation was provided for parafascicular nucleus. T... more A behavioral analysis of intracranial self-stimulation was provided for parafascicular nucleus. To evaluate whether intracranial self-stimulation in this nucleus could be site-specific and to determine if the positive sites are the same parafascicular areas that facilitate learning when stimulated, rats were tested via monopolar electrodes situated throughout the parafascicular nucleus. Animals were trained to self-stimulate by pressing a lever in a conventional Skinner box (1-5 sessions). Twenty-two of the 42 animals included in the study, had the electrode at the parafascicular nucleus. Only two of them showed intracranial self-stimulation. Histological analyses indicated that the latter rats had the electrode implanted at the anterior area of the medial parafascicular. Other two animals also showed intracranial self-stimulation but they had the electrode in a more posterior brain region, between the Dark-schewitsch nucleus and the red nucleus. The animals implanted at the parafascicular showed higher response rates than the other two rats. These results confirm that: (a) the anterior region of the medial parafascicular is a positive site for stable and regular intracranial self-stimulation behavior, and (b) these positive sites do not coincide with the parafascicular regions related to learning improvement.
Involvement of the parafascicular nucleus in the facilitative effect of intracranial self-stimulation on active avoidance in rats
Brain Research, 1998
To evaluate whether parafascicular nucleus (PF) is involved in the facilitative effect of lateral... more To evaluate whether parafascicular nucleus (PF) is involved in the facilitative effect of lateral hypothalamic intracranial self-stimulation (LH-ICSS) on two-way active avoidance acquisition (5 sessions, 10 trials each, one daily) and long-term retention (10 days), rats were lesioned bilaterally at the PF and implanted with an electrode aimed at the LH to obtain ICSS behavior. After each acquisition session rats were allowed to self-administer 2500 trains of LH-ICSS. The main results were: (1) LH-ICSS facilitated the acquisition and retention of conditioning; (2) PF lesions impaired both acquisition and retention of two-way active avoidance; (3) there was a positive relationship between PF lesions size and learning disruption, and (4) LH-ICSS failed to facilitate learning when PF was lesioned. We concluded that the lesion size is a critical variable to evaluate the effects of PF lesions on learning and memory, and that LH-ICSS treatment may exert their effects through the PF nucleus or, at least, the integrity of PF is required for LH-ICSS to improve clearly the task.
Improvement of shuttle-box avoidance with post-training intracranial self-stimulation, in rats: a parametric study
Behavioural Brain Research, 1991
Rats were trained in a two-way active avoidance task followed immediately by a lateral hypothalam... more Rats were trained in a two-way active avoidance task followed immediately by a lateral hypothalamic intracranial self-stimulation (ICSS) treatment, during 5 consecutive days. The effects of the number of ICSS trains allowed (0, 500, 2500 or 4500) were studied upon acquisition and long-term retention (LTR, 10 and 30 days). The number of ICSS trains administered and the number of avoidances at the last acquisition session (5th) showed a positive lineal relation, that is, the more number of ICSS trains, the more number of avoidances. The level of learning achieved during the 5th session was maintained after the LTR periods in all experimental groups. It is concluded that the number of ICSS trains could be a critical parameter in the facilitatory effect of lateral hypothalamic ICSS upon learning, and it is suggested that the facilitatory effect of post-training lateral hypothalamic ICSS might be due to the activation of general activatory neural systems.
Behavioural Brain Research, 2002
To evaluate possible differential effects of lateral hypothalamic intracranial self-stimulation (... more To evaluate possible differential effects of lateral hypothalamic intracranial self-stimulation (ICSS) on memory consolidation and retrieval, independent groups of Wistar rats were trained in a single session of two-way active avoidance task (acquisition session) and tested 24 h later (retention session). The post-ICSS groups received an ICSS treatment immediately after the acquisition session, and the pre-ICSS groups received the same treatment immediately before the retention session. Because the ICSS effects on memory seem to be dependent on the initial performance level shown by the subjects, the possible influence of initial training (number of trials) on ICSS effects was also studied. Therefore, we used different control and experimental groups, which received either 30 or 50 trials in the acquisition session. Post-training ICSS facilitated the 24-h retention in both training conditions (30 and 50 trials). In contrast, pre-retention ICSS treatment did not facilitate performance in the retention test. We also observed that post-training ICSS was more effective for improving the 24-h retention than increasing the initial training from 30 to 50 trials. This findings confirm that ICSS treatment improves memory consolidation and suggest that it might not affect memory retrieval mechanisms.
Behavioural Brain Research, 2005
Previous research has shown that post-training intracranial self-stimulation facilitates implicit... more Previous research has shown that post-training intracranial self-stimulation facilitates implicit or procedural memory. To know whether it can also facilitate explicit memory, post-training intracranial self-stimulation was given to Wistar rats immediately after every daily session of a delayed spatial alternation task that seems to depend on the integrity of the hippocampal memory system. We tested the effects of intracranial self-stimulation in three consecutive learning phases which tried to make the task progressively more difficult: 10 s delay (D10 phase), 30 s delay (D30 phase), and inverting the starting position of the animals to make their response more dependent on allocentric cues (INV phase). Every phase finished when each rat achieved a fixed learning criterion. Intracranial self-stimulation facilitated the flexible expression of the learned response (INV phase). That is, when the starting position was randomly inverted, only the rats that received intracranial self-stimulation maintained the performance level acquired in the previous training phases. Changing the starting position reduced the correct performance of the non-treated subjects, which need more training sessions to achieve the learning criterion and made less correct responses than treated rats. These findings show that post-training intracranial self-stimulation can facilitate hippocampus-dependent memories. SS has been shown to have the same positive effect on memory as increasing training . As far we know, the facilitative effect of SS has only been observed in implicit or procedural memory tasks, such as sensory pre-conditioning [6], aversive and appetitive classical conditioning or passive and active avoidance , but the effect of post-training SS on an explicit or declarative task has not been tested. Cahill and McGaugh [4] have pointed out that emotions, a natural way of arousal system activation, modulate the formation of both declarative and non-declarative memories. Therefore, it seems likely that the artificial cortical and subcortical arousal produced by SS could also facilitate declarative or explicit memory. The present experiment was designed to test this hypothesis. 0166-4328/$ -see front matter
Behavioural Brain Research, 1996
To evaluate whether the tuberomammillary nucleus might be involved in the acquisition and/or rete... more To evaluate whether the tuberomammillary nucleus might be involved in the acquisition and/or retention of a two-way active avoidance conditioning, rats were given a unilateral lesion of the tuberomammillary nucleus (E2 region) 24 h prior to the first conditioning session. Four learning sessions were performed: one acquisition and 3 retention sessions (short-term, 24 h; and long-term, 8 and 18 days). Results showed that the lesion facilitated the long-term retention of conditioning, but no effects were observed on acquisition and short-term retention. Since rewarding intracranial electrical stimulation seems to be a consistent way to facilitate learning and memory processes, and tuberomammillary lesion has been shown to improve intracranial self-stimulation behavior (ICSS), we suggest that lesions in the present experiment could have facilitated two-way active avoidance retention by enhancing the function of brain reward mechanisms.
Intracranial self-stimulation facilitates active-avoidance retention and induces expression of c-Fos and Nurr1 in rat brain memory systems
Behavioural Brain Research, 2013
Intracranial self-stimulation (ICSS), a special form of deep brain stimulation in which subjects ... more Intracranial self-stimulation (ICSS), a special form of deep brain stimulation in which subjects self-administered electrical stimulation in brain reward areas as the lateral hypothalamus, facilitates learning and memory in a wide variety of tasks. Assuming that ICSS improves learning and memory increasing the activation of memory-related brain areas, the present work examined whether rats receiving an ICSS treatment immediately after the acquisition session of a two-way active avoidance conditioning (TWAA) show both an improved retention and a pattern of increased c-Fos and Nurr1 protein expression in the amygdala, hippocampus, dorsal striatum and/or lateral hypothalamus. The response of both activity-induced IEGs to ICSS was examined not only as markers of neural activation, but because of their reported role in the neural plasticity occurring during learning and memory formation. Results showed that the TWAA conditioning alone increased the expression of the two analysed IEGs in several hippocampal areas, and TWAA retention increased Nurr1 expression in amygdala. ICSS treatment increased the number of c-Fos and Nurr1 positive cells in almost all the brain regions studied when it was measured 70min, but not 48h, after the stimulation. Post-training ICSS treatment, as expected, facilitated the 48h retention of the conditioning. It is noteworthy that in CA3 conditioning and ICSS separately increased c-Fos expression, but this increasing was greater when both, conditioning and ICSS, were combined. Present results suggest that rapid and transient increased expression of these two synaptic plasticity and memory related IEGs in some hippocampal areas, such as CA3, could mediate the facilitative effects of ICSS on learning and memory consolidation.
Shuttle-box memory facilitation by posttraining intracranial self-stimulation: Differential effects in rats with high and low basic conditioning levels
Behavioral Neuroscience, 1996
The effects of intracranial self-stimulation (ICSS) on retention (after 24 hr, 7, 15, or 60 days)... more The effects of intracranial self-stimulation (ICSS) on retention (after 24 hr, 7, 15, or 60 days) of a massed 2-way active avoidance task were studied in independent groups of rats. All groups showed a higher performance on the retention session than on the acquisition one. In the control subjects, the higher retention performances were observed in the 7- and 15-day groups. However, the ICSS treatment facilitated the 24-hr retention compared with its control group, allowing the treated subjects to achieve the same level of performance on the 24-hr retention session than that achieved by the control rats at the 7-day retention test. In the 24-hr groups, the facilitatory ICSS effect was stronger in the subjects with a low level of conditioning and weaker in those with a high level. Results suggest that posttraining ICSS accelerates memory consolidation and equalizes the performance of poor and good learners.
Correlations between paradoxical sleep and shuttle-box conditioning in rats
Behavioral Neuroscience, 1989
Eighteen male Wistar rats were given one daily two-way active avoidance conditioning session foll... more Eighteen male Wistar rats were given one daily two-way active avoidance conditioning session followed immediately by 5 hr of sleep recording, for 5 consecutive days. The group of rats that achieved 80% or greater avoidance in some of the 5 training sessions showed significant linear increases of paradoxical sleep (PS), compared with baseline levels, throughout the successive conditioning sessions. Furthermore, (a) the group of rats showing PS increases (more than 1 SD above baseline) after some of the training sessions achieved a significantly higher final number of avoidances than the remaining animals: (b) a high and positive correlation was observed between avoidance increases in the 3rd conditioning session and previous PS; and (c) maximum increases in correct performance often occurred following high PS increases. It is concluded that PS increases facilitate the consolidation of learning.
Behavioral Neuroscience, 2003
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Papers by Pilar Segura-torres