Two-way Active Avoidance Learning Research Articles

State Transitions During Discrimination Learning in the Gerbil Auditory Cortex Analyzed by Network Causality Metrics.

This work studies the evolution of cortical networks during the transition from escape strategy to avoidance strategy in auditory discrimination learning in Mongolian gerbils trained by the well-established two-way active avoidance learning paradigm. The animals were implanted with electrode arrays centered on the surface of the primary auditory cortex and electrocorticogram (ECoG) recordings were made during performance of an auditory Go/NoGo discrimination task. Our experiments confirm previous results on a sudden behavioral change from the initial naïve state to an avoidance strategy as learning progresses. We employed two causality metrics using Granger Causality (GC) and New Causality (NC) to quantify changes in the causality flow between ECoG channels as the animals switched to avoidance strategy. We found that the number of channel pairs with inverse causal interaction significantly increased after the animal acquired successful discrimination, which indicates structural changes in the cortical networks as a result of learning. A suitable graph-theoretical model is developed to interpret the findings in terms of cortical networks evolving during cognitive state transitions. Structural changes lead to changes in the dynamics of neural populations, which are described as phase transitions in the network graph model with small-world connections. Overall, our findings underscore the importance of functional reorganization in sensory cortical areas as a possible neural contributor to behavioral changes.

Effects of a methanol extract of Ficus platyphylla stem bark on a two-way active avoidance task and on body core temperature

Preparations of Ficus platyphylla are used in Nigeria’s folk medicine to manage a variety of diseases, including insomnia, psychoses, depression, epilepsy, pain, and inflammation. In this study, we examined the effects of the standardised methanol extract of F. platyphylla stem bark (FP) on two-way active avoidance learning and body core temperature to complement earlier studies on the neuroleptic potential of this medicinal plant, which is already in common use. The extract did not interfere with the acquisition and consolidation of the conditioned avoidance reaction (CAR), but did diminish the retrieval of CAR. The extract dose-dependently reduced body core temperature; this was significantly ameliorated by the use of amphetamine. The results confirmed the neuroleptic-like efficacy of FP, probably via the modulation of dopaminergic neurons.

Infant avoidance training alters cellular activation patterns in prefronto-limbic circuits during adult avoidance learning: II. Cellular imaging of neurons expressing the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1).

Positive and negative feedback learning is essential to optimize behavioral performance. We used the two-way active avoidance (TWA) task as an experimental paradigm for negative feedback learning with the aim to test the hypothesis that neuronal ensembles activate the activity-regulated cytoskeletal (Arc/Arg3.1) protein during different phases of avoidance learning and during retrieval. A variety of studies in humans and other animals revealed that the ability of aversive feedback learning emerges postnatally. Our previous findings demonstrated that rats, which as infants are not capable to learn an active avoidance strategy, show improved avoidance learning as adults. Based on these findings, we further tested the hypothesis that specific neuronal ensembles are "tagged" during infant TWA training and then reactivated during adult re-exposure to the same learning task. Using cellular imaging by immunocytochemical detection of Arc/Arg3.1, we observed that, compared to the untrained control group, (1) only in the dentate gyrus the density of Arc/Arg3.1-expressing neurons was elevated during the acquisition phase of TWA learning, and (2) this increase in Arc/Arg3.1-expressing neurons was not specific for the TWA learning task. With respect to the effects of infant TWA training we found that compared to the naïve non-pretrained group (a) the infant pretraining group displayed a higher density of Arc/Arg3.1-expressing neurons in the anterior cingulate cortex during acquisition on training day 1, and (b) the infant pretraining group displayed elevated density of Arc/Arg3.1-expressing neurons in the dentate gyrus during retrieval on test day 5. Correlation analysis for the acquisition phase revealed for the ACd that the animals which showed the highest number of avoidances and the fastest escape latencies displayed the highest density of Arc/Arg3.1-expressing neurons. Taken together, we are the first to use the synaptic plasticity protein Arc/Arg3.1 to label neuronal ensembles which are involved in different phases of active avoidance learning and whose activity patterns are changing in response to previous learning experience during infancy. Our results indicate (1) that, despite the inability to learn an active avoidance response in infancy, lasting memory traces are formed encoding the subtasks that are learned in infancy (e.g., the association of the CS and UCS, escape strategy), which are encoded in the infant brain by neuronal ensembles, which alter their synaptic connectivity via activation of specific synaptic plasticity proteins such as Arc/Arg3.1 and Egr1, and (2) that during adult training these memories can be retrieved by reactivating these neuronal ensembles and their synaptic circuits and thereby accelerate learning.

Paradoxical influence of combined effect of Semax and ammonium molybdate on learning and memory in rats

The combined effect of Semax with water solutions of plumbum diacetate (10–7 M) and ammonium molybdate (10–5 M) on the two-way active avoidance learning in rats in the shuttle chamber was studied. It was established that both salts of heavy metals oppress the learning and memory; plumbum diacetate caused larger oppression. Semax slowed down the development of the conditioned response but counteracted the negative influence on this process from the side of both metals. The effect of Semax on the development of the avoidance reaction in the presence of ammonium molybdate, which oppressed the avoidance by itself, paradoxically intensified. During the combined effect of the peptide and ammonium molybdate, the development of the conditioned reaction occurred much faster than against the background of Semax without the combination with molybdenum. In total, data obtained indicate a counteraction of Semax to neurotoxic effect of plumbum and molybdenum salts. Since oxidative stress is the main mechanism of neurotoxic effect of heavy metals, the indicated positive effect of Semax can, in our opinion, confirm the presence of antioxidant properties in the spectrum of the peptide pharmacological activity.

Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats.

Recent evidence has revealed the impact of exercise in alleviating anxiety and mood disorders; however, the exercise protocol that exerts such benefit is far from known. The current study was aimed to assess the effects of long-term moderate exercise on behavioural coping strategies (active vs. passive) and Hypothalamic-Pituitary-Adrenal response in rats. Sprague-Dawley male and female rats were exposed to 32-weeks of treadmill exercise and then tested for two-way active avoidance learning (shuttle-box). Two groups were used as controls: a non-handled sedentary group, receiving no manipulation, and a control group exposed to a stationary treadmill. Female rats displayed shorter escape responses and higher number of avoidance responses, reaching criterion for performance earlier than male rats. In both sexes, exercise shortened escape latencies, increased the total number of avoidances and diminished the number of trials needed to reach criterion for performance. Those effects were greater during acquisition in female rats, but remained over the shuttle-box sessions in treadmill trained male rats. In females, exercise did not change ACTH and corticosterone levels after shuttle-box acquisition. Collectively, treadmill exercise improved active coping strategies in a sex-dependent manner. In a broader context, moderate exercise could serve as a therapeutic intervention for anxiety and mood disorders.

Differential effects of wake promoting drug modafinil in aversive learning paradigms.

Modafinil (MO) an inhibitor of the dopamine transporter was initially approved to treat narcolepsy, a sleep related disorder in humans. One interesting “side-effect” of this drug, which emerged from preclinical and clinical studies, is the facilitation of cognitive performance. So far, this was primarily shown in appetitive learning paradigms, but it is yet unclear whether MO exerts a more general cognitive enhancement effect. Thus, the aim of the present study in rats was to extend these findings by testing the effects of MO in two aversive paradigms, Pavlovian fear conditioning (FC) and the operant two-way active avoidance (TWA) learning paradigms. We discovered a differential, task-dependent effect of MO. In the FC paradigm MO treated rats showed a dose-dependent enhancement of fear memory compared to vehicle treated rats, indicated by increased context-related freezing. Cue related fear memory remained unaffected. In the TWA paradigm MO induced a significant decrease of avoidance responses compared to vehicle treated animals, while the number of escape reactions during the acquisition of the TWA task remained unaffected. These findings expand the knowledge in the regulation of cognitive abilities and may contribute to the understanding of the contraindicative effects of MO in anxiety related mental disorders.

Sex-specific positive and negative consequences of avoidance training during childhood on adult active avoidance learning in mice

In humans and animals cognitive training during childhood plays an important role in shaping neural circuits and thereby determines learning capacity later in life. Using a negative feedback learning paradigm, the two-way active avoidance (TWA) learning, we aimed to investigate in mice (i) the age-dependency of TWA learning, (ii) the consequences of pretraining in childhood on adult learning capacity and (iii) the impact of sex on the learning paradigm in mice. Taken together, we show here for the first time that the beneficial or detrimental outcome of pretraining in childhood depends on the age during which TWA training is encountered, indicating that different, age-dependent long-term “memory traces” might be formed, which are recruited during adult TWA training and thereby either facilitate or impair adult TWA learning. While pretraining during infancy results in learning impairment in adulthood, pretraining in late adolescence improved avoidance learning. The experiments revealed a clear sex difference in the group of late-adolescent mice: female mice showed better avoidance learning during late adolescence compared to males, and the beneficial impact of late-adolescent pretraining on adult learning was more pronounced in females compared to males.

Stress inoculation facilitates active avoidance learning of the semi-precocial rodent Octodon degus

A growing body of evidence highlights the impact of the early social environment for the adequate development of brain and behavior in animals and humans. Disturbances of this environment were found to be both maladaptive and adaptive to emotional and cognitive function. Using the semi-precocial, biparental rodent Octodon degus, we aimed to examine (i) the impact of age (juvenile/adult), sex (male/female), and (ii) “motivation” to solve the task (by applying increasing foot-shock-intensities) on two-way active avoidance (TWA) learning in socially reared degus, and (iii) whether early life stress inoculation by 1h daily parental separation during the first three weeks of life has maladaptive or adaptive consequences on cognitive function as measured by TWA learning. Our results showed that (i) juvenile degus, unlike altricial rats of the same age, can successfully learn the TWA task comparable to adults, and (ii) that learning performance improves with increasing “task motivation”, irrespective of age and sex. Furthermore, we revealed that (iii) stress inoculation improves avoidance learning, particularly in juvenile males, quantitatively and qualitatively depending on “task motivation”.In conclusion, the present study describes for the first time associative learning in O. degus and its modulation by early life stress experience as an animal model to study the underlying mechanisms of learning and memory in the stressed and unstressed brain. Although, stress is commonly viewed as being maladaptive, our data indicate that early life stress inoculation triggers developmental cascades of adaptive functioning, which may improve cognitive and emotional processing of stressors later in life.

Differential Neuromodulation of Acquisition and Retrieval of Avoidance Learning by the Lateral Habenula and Ventral Tegmental Area

Several studies suggest an opponent functional relationship between the lateral habenula (LHb) and the ventral tegmental area (VTA). Previous work has linked LHb activation to the inhibition of dopaminergic neurons during loss of reward, as well as to deficits in escape and avoidance learning. We hypothesized that a dopamine signal might underlie the negative reinforcement of avoidance responses and that LHb activation could block this signal and thereby cause avoidance deficits. To test this idea, we implanted stimulating electrodes in either the VTA or LHb of gerbils engaged in two-way active avoidance learning, a task that shows learning-associated dopamine changes and that is acquired faster following LHb lesions. We delivered brief electrical brain stimulation whenever the animal performed a correct response, i.e., when the successful avoidance of foot shock was hypothesized to trigger an intrinsic reward signal. During the acquisition phase, VTA stimulation improved avoidance performance, while LHb stimulation impaired it. VTA stimulation appeared to improve both acquisition and asymptotic performance of the avoidance response, as VTA-stimulated animals reached above-normal performance but reverted to normal responding when stimulation was discontinued. The effects of LHb stimulation during avoidance acquisition were long lasting and persisted even after stimulation was discontinued. However, when given after successful acquisition of avoidance behavior, LHb stimulation had no effect, indicating that LHb stimulation specifically impaired avoidance acquisition without affecting memory retrieval or motivation or ability to perform the avoidance response. These results demonstrate opponent roles of LHb and VTA during acquisition but not during retrieval of avoidance learning.

Impaired active avoidance learning in infant rats appears to be related to insufficient metabolic recruitment of the lateral septum

The temporal dissociation between early information acquisition and output of complex behaviors is a common principle during development. Thus, although infant rats are not able to generate sufficient avoidance behavior during two-way active avoidance (TWA) training they obviously deposit a certain “memory trace” ( Schäble, Poeggel, Braun, & Gruss, 2007). The ontogeny of learning is probably mirrored by the maturing functionality of different basal forebrain regions. Two of the basal forebrain regions involved in TWA learning are the medial septum/diagonal band of Broca (MS/DB), which is essential for the encoding and retrieval of memory and the lateral septum (LS) that plays a role in the generation of behavior. Mapping 2-fluoro-deoxy-glucose utilization in freely behaving animals, the aim of this study was to assess the functional recruitment of the MS/DB and LS in infant (P17–P21) and adolescent (P38–P42) rats during the first (acquisition) and fifth (retrieval) TWA training. Metabolic activity in the MS/DB was similar in both age groups during acquisition and retrieval indicating that this region is already mature in the infant rat. In contrast, metabolic activity in the LS was generally lower in the infant rats suggesting that this region is not yet fully functional during P17 and P21. This insufficient recruitment may be one reason for the poor TWA performance of infant rats. Finally, the LS displayed significantly higher activity during acquisition than during retrieval indicating that the highest amount of energy is consumed during the initial learning phase.

Two-way active avoidance memory consolidation in rats with scopolamine infusions in basolateral amygdala and ventral hippocampus

Event Abstract Back to Event Two-way active avoidance memory consolidation in rats with scopolamine infusions in basolateral amygdala and ventral hippocampus Pere Boadas-Vaello1*, Anna Carballo-Marquez1, Irene Villarejo-Rodríguez1, Anna Vale-Martinez1, Gemma Guillazo-Blanch1 and Margarita Marti-Nicolovius1 1 Universitat Autònoma de Barcelona, Institut de Neurociències, Spain There is evidence that the muscarinic activity in several brain regions modulates memory formation of aversively-motivated tasks, although the involvement of the muscarinic receptors (mRs) in the consolidation of two-way active avoidance (TWAA) learning has not been examined. The aim of the present study was to investigate whether the blockade of mRs in the basolateral amygdala (BLA) or ventral hippocampus (vHPC), which receive important cholinergic projections and are involved in aversive learning, affects TWAA consolidation. Immediately after a 30-trial acquisition session (conditioned stimulus: 3-s 60-dB tone, unconditioned stimulus: 0.5-mA footshock), Wistar rats were bilaterally infused with scopolamine (20ìg/site) or phosphate-buffered saline in the BLA or vHPC. Twenty-four hours later, avoidance retention was tested in a 30-trial session. Results showed that there was no difference between the vehicle and scopolamine-injected rats in any measure of shuttle-box performance, indicating that mRs blockade produces no impairment in early memory formation of TWAA learning. Results are discussed in the context of possible occurrence of over-training, which may have a protective effect against scopolamine induced-memory deficits. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Boadas-Vaello P, Carballo-Marquez A, Villarejo-Rodríguez I, Vale-Martinez A, Guillazo-Blanch G and Marti-Nicolovius M (2009). Two-way active avoidance memory consolidation in rats with scopolamine infusions in basolateral amygdala and ventral hippocampus. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.095 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Jun 2009; Published Online: 08 Jun 2009. * Correspondence: Pere Boadas-Vaello, Universitat Autònoma de Barcelona, Institut de Neurociències, Barcelona, Spain, margarita.marti@uab.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Pere Boadas-Vaello Anna Carballo-Marquez Irene Villarejo-Rodríguez Anna Vale-Martinez Gemma Guillazo-Blanch Margarita Marti-Nicolovius Google Pere Boadas-Vaello Anna Carballo-Marquez Irene Villarejo-Rodríguez Anna Vale-Martinez Gemma Guillazo-Blanch Margarita Marti-Nicolovius Google Scholar Pere Boadas-Vaello Anna Carballo-Marquez Irene Villarejo-Rodríguez Anna Vale-Martinez Gemma Guillazo-Blanch Margarita Marti-Nicolovius PubMed Pere Boadas-Vaello Anna Carballo-Marquez Irene Villarejo-Rodríguez Anna Vale-Martinez Gemma Guillazo-Blanch Margarita Marti-Nicolovius Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Activation of phasic pontine‐wave generator in the rat: a mechanism for expression of plasticity‐related genes and proteins in the dorsal hippocampus and amygdala

A number of behavioral studies have emphasized the importance of interactions between the pontine-wave (P-wave) generator and the dorsal hippocampus (DH) in two-way active avoidance (TWAA) memory processing; however, the direct involvement of the P-wave generator in the TWAA training trial-induced molecular events in the DH and amygdala has not been systematically evaluated. Here we demonstrate that the TWAA learning training trials activate P-wave generator, and increase phosphorylation of CREB (pCREB) and expression of activity-regulated cytoskeletal-associated (Arc) protein, as well as messenger ribonucleic acid (mRNAs) of Arc, brain-derived nerve growth factor (BDNF) and early growth response-1 (Egr-1) in the DH and amygdala. Selective elimination of P-wave-generating cells abolished P-wave activity and suppressed TWAA learning training trial-induced expression of pCREB and Arc proteins and Arc, BDNF and Egr-1 mRNAs in the DH and amygdala. Following a session of TWAA training, all rats were equal in terms of time spent in wakefulness, slow-wave sleep and rapid eye movement (REM) sleep irrespective of P-wave lesions. The second set of experiments demonstrated that localized cholinergic stimulation of the P-wave generator increased expression of Arc, BDNF and Egr-1 mRNAs in the DH. Together, these findings provide the first direct evidence that activation of P-wave-generating cells is critically involved in the TWAA training trial-induced expression of plasticity-related genes in the DH and amygdala. These findings are discussed in relation to the role of P-wave generator activation for the REM sleep-dependent development and cognitive functions of the brain.

Long-term consequences of early experience on adult avoidance learning in female rats: Role of the dopaminergic system

Following our hypothesis that juvenile emotional and/or cognitive experience should affect learning performance at preweaning age as well as adulthood, the present study in female Wistar rats aimed to examine the impact of (i) avoidance training at preweaning age, (ii) exposure to repeated maternal separation, (iii) the combination of both, and (iv) the blockade of dopaminergic neurotransmission on adult two-way active avoidance learning in rats. We found that preweaning, i.e. three week old, rats were less capable of avoidance learning compared to adults. Our main findings revealed that preweaning avoidance training alone improved avoidance learning in adulthood. Furthermore, maternal separation alone also improved avoidance learning in preweaning and in adult rats, but this effect of maternal separation did not add up to the beneficial effect of preweaning avoidance training on adult learning. In addition, the pharmacological blockade of dopamine receptors during preweaning avoidance training via systemic application of haloperidol impaired preweaning avoidance performance in a dose-dependent manner. Testing the haloperidol-treated preweaning presumed “non-learners” as adults revealed that they still showed improved learning as adults. Taken together, our results strongly support the hypothesis that emotional as well as cognitive experience at preweaning age leaves an enduring “memory trace,” which can facilitate learning in adulthood. Our pharmaco-behavioral studies suggest that unlike the adult brain, preweaning learning and memory formation is less dependent on dopaminergic mechanisms, which raises the intriguing question of possible alternative pathways.

Two‐way active avoidance training‐specific increases in phosphorylated cAMP response element‐binding protein in the dorsal hippocampus, amygdala, and hypothalamus

Previous studies have demonstrated that the activation of pontine-wave (P-wave) generating cells in the brainstem during post-training rapid eye movement (REM) sleep is critical for the consolidation of memory for two-way active avoidance (TWAA) learning in the rat. Here, using immunocytochemistry, we investigated the spatio-temporal distribution of CREB phosphorylation within different parts of the dorsal hippocampus, amygdala, and hypothalamus following a session of TWAA training in the rat. We show that the TWAA training trials increased phosphorylation of CREB (p-CREB) in the dorsal hippocampus, amygdala, amygdalo-hippocampal junction (AHi), and hypothalamus. However, the time intervals leading to training-induced p-CREB activity were different for different regions of the brain. In the dorsal hippocampus, p-CREB activity was maximal at 90 min and this activity disappeared by 180 min. In the AHi, activity of the p-CREB peaked by 180 min and disappeared by 360 min. In the amygdala, the p-CREB activity peaked at 180 min and still remained higher than the control at the 360 min interval. In the hypothalamus, at 90 min p-CREB activity was present only in the ventromedial hypothalamus; however, by 180 min this p-CREB activity was also present in the dorsal hypothalamus, perifornical area, and lateral hypothalamus. By 360 min, p-CREB activity disappeared from the hypothalamus. This TWAA training trials-induced spatiotemporal characteristic of CREB phosphorylation, for the first time, suggests that REM sleep P-wave generator activation-dependent memory processing involves different parts of the dorsal hippocampus, amygdala, and hypothalamus.

Pontine‐wave generator activation‐dependent memory processing of avoidance learning involves the dorsal hippocampus in the rat

The aim of this study was to test the hypothesis that the dorsal hippocampus plays a critical role in pontine-wave (P-wave) generator activation-dependent memory processing of two-way active avoidance (TWAA) learning. To achieve this objective, rats were given small bilateral lesions in the CA1, dentate gyrus (DG), or CA3 region of the dorsal hippocampus by microinjecting ibotenic acid. After recovery, lesioned and sham-lesioned rats were trained on a TWAA learning paradigm, allowed a 6-hr period of undisturbed sleep, and then were tested on the same TWAA paradigm. It was found that lesions in the CA3 region impaired retention of avoidance learning. Conversely, lesions in the CA1 and DG regions had no effect on TWAA learning retention. None of the groups showed any changes in the baseline sleep-wake cycle or in the acquisition of TWAA learning. All rats showed increased rapid eye movement (REM) sleep and increased REM sleep P-wave density during the subsequent 6-hr recording period. Impaired retention in the CA3 group occurred despite an increase in REM sleep and P-wave density, suggesting that during REM sleep, the P-wave generator interacts with the CA3 region of the dorsal hippocampus to aid in consolidation of TWAA learning. The results of the present study thus demonstrate that P-wave generator activation-dependent consolidation of memory requires an intact CA3 subfield of the dorsal hippocampus. The results also provide evidence that under mnemonic pressure, the dorsal hippocampus may not be involved directly in regulating the sleep-wake cycle.

Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats

Based on clues from epidemiology, low prenatal vitamin D has been proposed as a candidate risk factor for schizophrenia. Recent animal experiments have demonstrated that transient prenatal vitamin D deficiency is associated with persistent alterations in brain morphology and neurotrophin expression. In order to explore the utility of the vitamin D animal model of schizophrenia, we examined different types of learning and memory in adult rats exposed to transient prenatal vitamin D deficiency. Compared to control animals, the prenatally deplete animals had a significant impairment of latent inhibition, a feature often associated with schizophrenia. In addition, the deplete group was (a) significantly impaired on hole board habituation and (b) significantly better at maintaining previously learnt rules of brightness discrimination in a Y-chamber. In contrast, the prenatally deplete animals showed no impairment on the spatial learning task in the radial maze, nor on two-way active avoidance learning in the shuttle-box. The results indicate that transient prenatal vitamin D depletion in the rat is associated with subtle and discrete alterations in learning and memory. The behavioural phenotype associated with this animal model may provide insights into the neurobiological correlates of the cognitive impairments of schizophrenia.

Complex effects of NMDA receptor antagonist APV in the basolateral amygdala on acquisition of two-way avoidance reaction and long-term fear memory.

Although much has been learned about the role of the amygdala in Pavlovian fear conditioning, relatively little is known about an involvement of this structure in more complex aversive learning, such as acquisition of an active avoidance reaction. In the present study, rats with a pretraining injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV), into the basolateral amygdala (BLA) were found to be impaired in two-way active avoidance learning. During multitrial training in a shuttle box, the APV-injected rats were not different from the controls in sensitivity to shock or in acquisition of freezing to contextual cues. However, APV injection led to impaired retention of contextual fear when tested 48 h later, along with an attenuation of c-Fos expression in the amygdala. These results are consistent with the role of NMDA receptors of the BLA in long-term memory of fear, previously documented in Pavlovian conditioning paradigms. The APV-induced impairment in the active avoidance learning coincided with deficits in directionality of the escape reaction and in attention to conditioned stimuli. These data indicate that normal functioning of NMDA receptors in the basolateral amygdala is required during acquisition of adaptive instrumental responses in a shuttle box but is not necessary for acquisition of short-term contextual fear in this situation.

Parafascicular electrical stimulation attenuates nucleus basalis magnocellularis lesion-induced active avoidance retention deficit

Previous experiments from our laboratory showed that retention of two-way active avoidance learning is improved by post-training intracranial electrical stimulation (ICS) of the parafascicular nucleus (PF) and impaired by pre-training electrolytic lesions of the nucleus basalis magnocellularis (NBM). The question investigated here was whether post-training PF ICS is able to attenuate the active avoidance retention deficit observed in rats lesioned pre-training in the NBM. To this goal, the following experimental design was used: rats bilaterally lesioned in the NBM and stimulated in the PF, rats lesioned in the NBM, rats stimulated in the PF, control rats implanted in the PF, and sham-operated rats were first trained in a shuttle-box for a single 30-trial session and tested again following two successive retention intervals (24 h and 11 days). The results showed that: (1) NBM lesions impaired the 11-day performance without affecting either the acquisition or the 24-h retention of the avoidance learning; (2) PF ICS treatment in unlesioned rats improved performance in both retention sessions only when the stimulation was applied in the posterior region of the nucleus; and (3) stimulation of the posterior PF compensated the 11-day retention impairment induced by NBM lesions. These results are discussed in relation to the interaction of arousal systems in the modulation of cognitive processes.

Activation of the phasic pontine-wave generator enhances improvement of learning performance: a mechanism for sleep-dependent plasticity.

The aim of this study was to test the hypothesis that supplementary activation of the phasic pontine wave (P-wave) generator during rapid eye movement (REM) sleep enhances consolidation and integration of memories, resulting in improved learning. To test this hypothesis, two groups of rats were trained on a two-way active avoidance learning task in the morning. Immediately after training, one group of rats received a carbachol microinjection into the P-wave generator and the other group was microinjected with control saline into the same target area. After training trials and microinjections, rats were allowed a 6-h period of undisturbed sleep in the polygraphic recording chamber. At the end of 6 h of undisturbed sleep-wake recordings, rats were retested in a session of avoidance learning trials. After learning trials, the total percentage of time spent in REM sleep was significantly increased in both saline (15.36%)- and carbachol (17.70%)-microinjected rats. After learning trials, REM sleep P-wave density was significantly greater throughout the 6-h period of recordings in carbachol treated rats than in the saline treated rats. In the retrial session, the improvement in learning task performance was 22.75% higher in the carbachol-microinjected rats than in the saline-microinjected rats. These findings show that the consolidation and integration of memories create a homeostatic demand for P-waves. In addition, these findings provide experimental evidence, for the first time, that activation of the P-wave generator may enhance consolidation and integration of memories, resulting in improved performance on a recently learned task.

The effects of telencephalic pallial lesions on spatial, temporal, and emotional learning in goldfish

In mammals, the pallial amygdala is implicated in emotional learning and memory, whereas the hippocampus is involved in spatial, contextual, or relational memory. This review presents a set of experiments aimed to study the involvement of the dorsomedial and dorsolateral telencephalon of goldfish in spatial and active avoidance learning. Results showed that (1) medial lesions impaired both acquisition and retention of conditioned avoidance response in two-way active avoidance learning experiments with stimuli overlapping (emotional factor) and with an interstimuli gap (temporal and emotional factors), and (2) the medial lesion did not affect spatial learning (spatial, contextual, or relational factors). In contrast, lateral lesions did not impair conditioned avoidance response with stimuli overlapping, but affected conditioned avoidance response with an interstimuli gap and spatial learning. These results support the presence of two differentiated memory systems in teleost fish based on discrete pallial regions: emotional (dorsomedial telencephalon) and spatial/temporal or relational (dorsolateral telencephalon). Furthermore, these functional data support the homology between the medial pallium of the teleost and the pallial amygdala of land vertebrates, and between the teleost lateral pallium and the mammalian hippocampus.