Prefrontal cortex or basolateral amygdala lesions blocked the stress-induced inversion of serial memory retrieval pattern in mice

Previous data from our team have shown that pre-test stress in mice reversed the pattern of memory retrieval in a contextual serial spatial task (CSD; Celerier, A., Pierard, C., Rachbauer, D., Sarrieau, A., & Beracochea, D. (2004). Contextual and serial discriminations: A new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice. Learning and Memory, 11, 196-204). The present study is aimed at determining brain areas which might be critically involved in mediating the stress effect on memory retrieval in the CSD task. For that purpose, we studied hereby the effects of ibotenic acid lesions of either the prefrontal cortex (PFC) or the basolateral amygdala (BLA) in Stressed or Non-Stressed Balb/c mice on memory retrieval in the CSD task. In that task, mice learned two successive spatial discriminations (D1 and D2) within two different internal contexts in a four-hole board. The stressor (electric footshocks) was delivered 5 min before test, occurring 24 h after acquisition. During test, mice were relocated either on the floor of the first or of the second discrimination. Results showed that (i) spatial memory was substantial and remained unaffected both by lesions and stress; (ii) Non-Stressed controls as well as Non-Stressed or Stressed PFC and BLA-lesioned mice remembered accurately D1 but not D2; and (iii) in contrast, Stressed controls accurately remembered D2 but not D1. In parallel to behavioral experiments, we also showed that PFC and BLA lesions did not affect the stress-induced increase of plasma corticosterone levels. All together, PFC and BLA integrity are not necessary for retrieval processes per se; in contrast, the PFC and BLA are critically involved in the mediation of the deleterious stress effects on serial order memory retrieval.     

Acute and chronic stress effects on performance in a forced-swim task

The effects of uncontrollable stressors on performance in a subsequent forced-swim paradigm were assessed in mice. Uncontrollable shock initially induced behavioral invigoration; however, within 24 h of stressor application, swimming behavior was depressed relative to nonstressed mice. The controllability of the stressor did not influence the initial invigoration, being present among escapably shocked mice as well as among mice that received (yoked) inescapable shock. In contrast, the depression of responding evident 24 h after stressor application was related to the availability of behavioral coping methods. Finally, following repeated exposure to footshock there was no indication of adaptation to the behavioral changes ordinarily induced by acute shock stress. The data were related to the effects of uncontrollable stressors on escape performance, and with respect to the use of this preparation as an animal model of human depression.     

Acute stress facilitates trace eyeblink conditioning in C57BL/6 male mice and increases the excitability of their CA1 pyramidal neurons

The effects of stress (restraint plus tail shock) on hippocampus-dependent trace eyeblink conditioning and hippocampal excitability were examined in C57BL/6 male mice. The results indicate that the stressor significantly increased the concentration of circulating corticosterone, the amount and rate of learning relative to nonstressed conditioned mice, and the excitability of CA1 hippocampal pyramidal neurons. Behaviorally, there was no effect of the stressor on control mice that received unpaired presentations of the tone and periorbital shock, i.e., neither stressed nor nonstressed control mice showed an increase in conditioned responding that was above baseline levels. Biophysically, the stressor significantly decreased the amplitude of the post-burst afterhyperpolarization (AHP) and decreased spike frequency accommodation relative to cells from nonstressed control mice. The effect was significant for mice that were stressed either 1 h or 24 h earlier. The results suggest that the stressor increases the excitability of hippocampal pyramidal neurons and that the mechanism underlying this increase may contribute to the more rapid acquisition of hippocampally dependent eyeblink conditioning.     

Discriminations among perceptual and symbolic stimuli

This research compares the time required for perceptual discriminations among pairs of physically present objects (circles) with the time required to discriminate pairs of symbols Inonsense syllables) that subjects learned to associate uniquely with each of the circles. Four experiments show very large differences between symbolic and perceptual discriminations. Discrimination times for the perceptual stimuli declined systematically as their size ratio increased, but discriminations among the associated nonsense syllables showed only a strictly ordinal effect of position in the series. Discriminations among the symbolic stimuli showed a large semantic congruity effect, but the perceptual stimuli showed none. The research does not replicate previous results showing similarities between perceptual and symbolic processing suggestive of image processing. We conclude that in the symbolic task subjects use only ordinal information rather than images or analog representations of the associated circles. We propose that perceptual discriminations show a semantic congruity effect only when they are processed as if the perceptual stimuli were symbolic.     

A revised spatial serial learning and memory procedure using Corsi's Block-tapping apparatus

The purpose of this study was to use Corsi's Block Tapping Test as a spatial analog of Benton's Serial Digit Learning Test, using the cognitive neuroscience approach utilized in the California Verbal Learning Test. 60 normal participants, ages 19-52 years, were included and administered an 8-block sequence for 9 trials or until they recalled the entire sequence for 3 consecutive errorless trials. The score was the number of blocks tapped in the correct serial order. An interference trial was administered. Following a 10-min. delay, free recall of the original sequence, cued recall, and recognition measures were obtained. Retroactive interference was significant, but no proactive interference emerged. Scores showed a strong primacy effect. Most participants who learned the sequence to the criterion of three successive errorless trials recalled the sequence after the 10-min. delay. Scores on the cued recall and recognition trials tended to support their validity as less demanding retrieval tasks. The use of this spatial learning and memory procedure allows finer discriminations among nonverbal memory deficits and may facilitate direct comparisons with scores on verbal memory tasks such as Serial Digit Learning and the California Verbal Learning Test.     

Timing matters: Temporal dynamics of stress effects on memory retrieval

Stress may impair memory retrieval. This retrieval impairment has been attributed to the action of the stress hormone cortisol, which is released with a delay of several minutes after a stressful encounter. Hence, most studies tested memory retrieval 20–30 min after stress, when the stress-induced cortisol increase peaks. In the present experiment, we investigated whether retrieval impairments can also be found at later intervals after stress. To this end, participants learned a list of words on day 1. Twenty-four hours later, they were first exposed to a stressor or a nonstressful control manipulation and completed a recognition test for the words either immediately thereafter, 25 min later, or 90 min later. Our findings showed that stress did not impair memory retrieval when memory was tested immediately after the stressor, before cortisol levels were elevated. However, retrieval performance was impaired 25 min after stress, when cortisol levels peaked, as well as 90 min after the stressor, when cortisol levels had already returned to baseline. The retrieval impairment 90 min after stress appeared to be even stronger than the one after 25 min. These findings suggest that the detrimental effects of stress on retrieval performance may last longer than is usually assumed.     

The hippocampus and prefrontal cortex are differentially involved in serial memory retrieval in non-stress and stress conditions

We previously showed that 24 h after learning, mice significantly remembered the first (D1) but not the second (D2) discrimination in a serial spatial task and that an acute stress delivered 5 min before the test phase reversed this memory retrieval pattern.A first experiment evaluated the effects of dorsal hippocampus (HPC) or prefrontal cortex (PFC) lesions, these two brain areas being well-known for their involvement in serial and spatial memory processes. For this purpose, six independent groups of mice were used: non-lesioned (controls), PFC or HPC-lesioned animals, submitted or not to an acute stress (electric footshocks; 0.9 mA). Results show that (i) non-stressed controls as well as PFC-lesioned mice (stressed or not) remembered D1 but not D2; (ii) stressed controls and HPC-lesioned mice (stressed or not) remembered D2 but not D1; (iii) stress significantly increased plasma corticosterone in controls and PFC-lesioned mice, but not in HPC-lesioned mice which already showed a significant plasma corticosterone increase in non-stressed condition.Since data from this first experiment showed that stress inhibited the hippocampal-dependent D1 memory retrieval, a second experiment evaluated the behavioral effect of intrahippocampal corticosterone injection in non-stressed mice. Results show that intrahippocampal corticosterone injection induced a reversal of serial memory retrieval pattern similar to that induced by acute stress.Overall, our study shows that (i) in non-stress condition, the emergence of D1 is HPC-dependent; (ii) in stress condition, the emergence of D2 requires the PFC integrity; moreover, intrahippocampal corticosterone injection mimicked the effects of stress in the CSD task.     

No Retrieval-Induced Forgetting Under Stress

ABSTRACT— Stress affects memory, yet no study has investigated the effects of stress on memory inhibition: Remembering not only facilitates later recall, but also inhibits retrieval of related material, a phenomenon known as retrieval-induced forgetting. We investigated the effects of stress on this mechanism, which is thought to adaptively guide memory selection. Participants learned categorized lists and were then exposed to either a psychosocial laboratory stressor or a cognitively challenging control treatment. They then actively retrieved parts of the previously learned material. Finally, memory for all initially learned items was tested. In the stress group, unlike in the control group, intervening retrieval practice did not impair final recall. Moreover, salivary cortisol levels increased and psychological well-being decreased in the stress group only. Thus, psychosocial stress abolishes retrieval-induced forgetting. This effect may result from stress-induced hormone release from the hypothalamic-pituitary-adrenal (HPA) axis and may have implications for educational, legal, and clinical issues.     

The effect of stress on inflammation

Stress can either enhance or suppress aspects of the immune response, depending on the nature, duration, timing and intensity of the stressor. This paper focuses on the effects on inflammation of two behavioural stress paradigms: learned helplessness (La) and the open-field test (OF), and of the immunological stressor lipopolysaccharide (LPS). We have observed that the onset and severity of inflammation in adjuvant-induced arthritis (AA) in the rat can be altered by experience of the LH paradigm, or by priming with LPS, but not by OF.In the LH test, some rats escape (LH(-)) and others do not (LH(+)). Despite the LH(-) group demonstrating a greater corticosterone response to the LH stressor compared to the LH(+)rats, they exhibited earlier onset and greater seventy of AA. In contrast, intraperitoneal injection of LPS several weeks prior to induction of AA protected against inflammation. These results provide further evidence that environmental factors influence the etiology of at least one type of inflammation. The modulation of inflammation by a defined stressor suggests that understanding of the underlying mechanisms may provide a potential for novel therapies.     

Acute stress impairs recognition for positive words--association with stress-induced cortisol secretion

Some studies suggest that stress-induced effects of cortisol on memory are modulated by the valence of the stimuli to be learned and retrieved. The present study investigated the effect of acute stress-induced cortisol secretion on acquisition and retrieval of pleasant, unpleasant and neutral words. Sixty healthy men were randomly assigned to one of the three experimental groups. Participants were either exposed to a standardized laboratory stressor (the Trier Social Stress Test) before learning a wordlist, or before retrieval, or were not stressed. Free recall and recognition were tested 24 h later. Free recall was not affected by stress exposure. For recognition, there was no main effect of the stressor, but a main effect of valence and a valence by group interaction emerged: recognition for positive words was significantly impaired when subjects were stressed before retrieval. In addition, a positive correlation between the cortisol response and errors of commission was found. The results suggest that acute stress impairs memory for positive stimuli and that stress-induced cortisol secretion interferes with accuracy of memory retrieval, i.e. the ability to discriminate true memories from false ones.     

Comparing patterning and biconditional discriminations in humans

In two experiments, human participants performed a causal judgment task that simultaneously comprised two reciprocal patterning discriminations and a biconditional discrimination. They learned both patterning discriminations more quickly than the biconditional discrimination. Postdiscrimination tests were used to identify participants who had, or had not, learned to apply the patterning rules, as well as participants who continued to expect summation when presented with two cues that predicted the same outcome. All groups were faster to learn the patterning than the biconditional discriminations. These results are inconsistent with models of stimulus representation that invoke configural representations (e.g., Pearce, 1987, 1994; Rescorla & Wagner, 1972) because these models solve biconditional discriminations more readily than patterning discriminations.     

An Experimental Investigation of the Effect of Stress on Saving and Acquiring Behavioral Tendencies: The Role of Distress Tolerance and Negative Urgency

Stress has been implicated as a risk factor for hoarding, although past research has relied on cross-sectional and self-report designs. Using experimental methods and objective hypothetical behavioral hoarding paradigms, we investigated the direct effect of stress on in-the-moment saving and acquiring behavioral tendencies. We also evaluated whether distress tolerance (DT) and negative urgency interacted with stress to predict saving and acquiring behavioral tendencies. A sample of young adults (N = 80) completed questionnaires about DT and negative urgency. Participants were randomized to either a psychosocial stressor or nonstressful control task prior to completing two hypothetical behavioral hoarding paradigms. The discarding task asked participants to choose between saving and disposing of items. For the acquiring task, participants completed a computer-simulated shopping spree that measured items acquired. Unexpectedly, participants in the stress condition saved and acquired fewer items than those in the control condition. As hypothesized, stress interacted with DT to predict saving tendencies. The current study should be replicated in a clinical sample. Longitudinal studies are needed to further examine the long-term effect of stress on hoarding. This is the first examination of the direct effect of stress on saving and acquiring tendencies. Although some study hypotheses were not supported, several results are consistent with our predictions and suggest a complex relationship between stress and hoarding. If findings are replicated in a clinical sample, it may be that hoarding patients could benefit from treatments incorporating DT strategies.     

Conditional discrimination in mentally retarded adults: the development of generalized skills.

The development of generalized conditional discrimination skills was examined in adults with retardation. Two subjects with histories of failure to acquire arbitrary matching under trial-and-error procedures were successful under procedures that trained one or more prerequisite skills. The successive discrimination between the sample stimuli was established by training the subjects to name the stimuli. The simultaneous discrimination between the comparison stimuli was established using either (a) standard simple discrimination training with reversals or (b) a procedure in which each of the two sample-comparison relations in the conditional discrimination was presented in blocks of trials, with the size of the blocks decreasing gradually until sample presentation was randomized. The amount of prerequisite training required varied across subjects and across successive conditional discriminations. After acquiring either two or three conditional discriminations with component training, both subjects learned new conditional discriminations under trial-and-error procedures. In general, each successive conditional discrimination was acquired more rapidly. Tests showed that conditional responding had become a generalized skill. Symmetry was shown for almost all trained relations. Symmetry trial samples were ultimately named the same as the stimuli to which they were related in training.     

Acquisition of categorical color perception: a perceptual learning approach to the linguistic relativity hypothesis

Color perception can be categorical: Between-category discriminations are more accurate than equivalent within-category discriminations. The effects could be inherited, learned, or both. The authors provide evidence that supports the possibility of learned categorical perception (CP). Experiment 1 demonstrated that observers' color discrimination is flexible and improves through repeated practice. Experiment 2 demonstrated that category learning simulates effects of "natural" color categories on color discrimination. Experiment 3 investigated the time course of acquired CP. Experiment 4 found that CP effects are acquired through hue- and lightness-based category learning and obtained interesting data on the dimensional perception of color. The data are consistent with the possibility that language may shape color perception and suggest a plausible mechanism for the linguistic relativity hypothesis.     

A computer touch-screen apparatus for training visual discriminations in rats.

We describe an operant conditioning apparatus that uses computerized touch-screen technology and is designed for the versatile and highly controlled testing of rats in a potentially wide variety of behavioral paradigms. Although computer-controlled touch-screen systems have been developed for use with pigeons, monkeys, and humans, analogous technologies and methods have not yet been developed for rats. The development of a touch-screen system for rats could enhance the efficiency of behavioral research with rats, and may offer a unique tool for studying animal learning. In the first test of the utility of the apparatus, 3 Sprague-Dawley rats learned to activate the touch screen only after the touch-screen panel was made slightly movable. These animals then learned to discriminate visual stimuli presented on the computer monitor, but only after the food magazine and pellet dispenser were moved to the rear of the chamber opposite the stimulus display and response window. In a test of the utility of the modified apparatus, 6 Long-Evans rats learned to activate the touch screen and learned one of three different simple discriminations using computer-generated, visually presented stimuli. A basic method for training rats to activate the computer touch screen and for visual discrimination training is described. Results show that rats learned to activate the touch screen and discriminate visual stimuli presented on a computer monitor. Potential applications and advantages of the touch-screen-equipped rat operant conditioning chamber are discussed.     

Benefit of social support for resilience-building is contingent on social context: examining cardiovascular adaptation to recurrent stress in women

Previous work on social support and stress tolerance using laboratory-based cardiovascular stress response paradigms has suggested that perceived social support may be effective in building resilience in recipients. However, such paradigms are often socially de-contextualized insofar as they fail to take account of the social aspects of stress itself. Using 90 healthy college women, the present study sought to examine the association between self-reported perceived social support and cardiovascular stress tolerance. Participants underwent two consecutive exposures to a mental arithmetic task. On second exposure to the stressor, participants completed the task under either social threat or control conditions. Social threat was manipulated using socially salient instructions, to create a high social context. Adaptation to stress was established in terms of comparisons between cardiovascular responses to successive exposures. Results showed that cardiovascular responses tended to habituate across time, with perceived social support associated with the degree of habituation, but only under certain contextual conditions; high perceived support was associated with effective habituation under control conditions only. This response pattern is consistent with the view that high perceived social support buffers against stress in healthful ways, but only in asocial contexts.     

Conditional discrimination in mentally retarded subjects: programming acquisition and learning set.

In Experiment 1, 3 subjects with retardation were exposed to two visual-visual arbitrary matching-to-sample problems each day. One conditional discrimination was presented under trial-and-error conditions, and the other was presented under a component training procedure. The latter began by establishing the comparison discrimination and its rapid reversal. The successive discrimination between the sample stimuli was established through differential naming. Then, sample naming was maintained in conditional discrimination sessions in which the same sample was presented in blocks of consecutive trials. Block size was decreased across sessions until sample presentation was randomized as in trial-and-error training (but with naming maintained). Two subjects initially learned only with component training. The performance of the 3rd subject was inconsistent across conditional discriminations. One of the successful subjects ultimately learned rapidly and consistently with trial-and-error procedures. Experiment 2 sought to demonstrate learning set in the other 2 subjects. Elements of the component training procedure were withdrawn over successive conditional discriminations. Ultimately, 1 subject nearly always learned under trial-and-error conditions, and the other learned under trial-and-error conditions combined with differential sample naming.     

Comparison Blindness

Change blindness has been linked to comparisons over time when visual input is disturbed by a transient. This is most directly seen in “flicker” paradigms where change is invisible when introduced during a blank period between successive presentations of stimuli, and is implicit in paradigms where a stimulus is changed during a saccade. Difficulties in comparing two simultaneously present stimuli have been considered to be due to transaccadic memory limitations in tasks requiring saccades. We present here experiments that demonstrate the phenomenology of change blindness, but in tasks where two stimuli are present in the central visual field within a single fixation and where there are no transients present. These experiments are based on contrast discriminations of patterns composed of a few simple elements. We have found comparisons over space within a single fixation to be as difficult as comparisons over time. As in the more usual paradigms for change blindness, cueing makes changes easy to detect. These results suggest that a memory bottleneck is not essential to produce change blindness.     

Impaired memory retrieval correlates with individual differences in cortisol response but not autonomic response

Stress can enhance or impair memory performance. Both cortisol release and sympathetic nervous system responses have been implicated in these differential effects. Here we investigated how memory retrieval might be affected by stress-induced cortisol release, independently of sympathetic nervous system stress responses. Thirty-two healthy participants (16 women) learned emotionally arousing and neutral words. One hour later, half of the participants underwent a stressor (cold pressor test) and the other half, a control warm water exposure, both followed by a delayed free recall task. The stressed participants were split into those who did (responders, N = 8) and those who did not (nonresponders, N = 6) show a cortisol response. Both responders and nonresponders showed comparable sympathetic nervous system activity (skin conductance level) during the cold pressor. The cortisol responders recalled significantly fewer words compared to nonresponders, and compared to control participants; this effect was most pronounced for moderately arousing words (compared to highly arousing and neutral words). These results suggest that individual differences in cortisol reactivity affect memory retrieval performance, and help to explain the differential effects of stress on memory.     

Serial learning: A multilevel access analysis

In Experiment I the lists were 36 and 48 unrelated words. Each was divided into successive groups of four words and learned to a perfect criterion. In Experiment II the lists were made up of six categorical groups of five exemplars each. Degree of learning was varied. In both experiments serial anticipation learning was followed by ordinary free recall and free recall under speed stress. Analyses of acquisition and of both recall tests indicate that group access is a marked function of serial position but that within-group retrieval given group access is constant over serial position. It is argued that serial learning proceeds simultaneously at different levels of representation.