Differential MR/GR Activation in Mice Results in Emotional States Beneficial or Impairing for Cognition

Corticosteroids regulate stress response and influence emotion, learning, and memory via two receptors in the brain, the high-affinity mineralocorticoid (MR) and low-affinity glucocorticoid receptor (GR). We test the hypothesis that MR- and GR-mediated effects interact in emotion and cognition when a novel situation is encountered that is relevant for a learning process. By adrenalectomy and additional constant corticosterone supplement we obtained four groups of male C57BL/6J mice with differential chronic MR and GR activations. Using a hole board task, we found that mice with continuous predominant MR and moderate GR activations were fast learners that displayed low anxiety and arousal together with high directed explorative behavior. Progressive corticosterone concentrations with predominant action via GR induced strong emotional arousal at the expense of cognitive performance. These findings underline the importance of a balanced MR/GR system for emotional and cognitive functioning that is critical for mental health

Post-Training Reward Partially Restores Chronic Stress Induced Effects in Mice

Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact) over the course of two weeks. Following novelty exploration, (non-) spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1) the effects of chronic stress persisted beyond the period of the actual rat exposure. (2) Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3) in stressed mice sugar partially “normalized” the impaired performance to the level of controls without sugar. Chronic stress (4) increased behavioral inhibition in response to novelty; (5) induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6) increased the intake of sucrose and water. (7) Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory

Stress Strengthens Memory of First Impressions of Others' Positive Personality Traits

Encounters with strangers bear potential for social conflict and stress, but also allow the formation of alliances. First impressions of other people play a critical role in the formation of alliances, since they provide a learned base to infer the other's future social attitude. Stress can facilitate emotional memories but it is unknown whether stress strengthens our memory for newly acquired impressions of other people's personality traits. To answer this question, we subjected 60 students (37 females, 23 males) to an impression-formation task, viewing portraits together with brief positive vs. negative behavior descriptions, followed by a 3-min cold pressor stress test or a non-stressful control procedure. The next day, novel and old portraits were paired with single trait adjectives, the old portraits with a trait adjective matching the previous day's behavior description. After a filler task, portraits were presented again and subjects were asked to recall the trait adjective. Cued recall was higher for old (previously implied) than the novel portraits' trait adjectives, indicating validity of the applied test procedures. Overall, recall rate of implied trait adjectives did not differ between the stress and the control group. However, while the control group showed a better memory performance for others' implied negative personality traits, the stress group showed enhanced recall for others' implied positive personality traits. This result indicates that post-learning stress affects consolidation of first impressions in a valence-specific manner. We propose that the stress-induced strengthening of memory of others' positive traits forms an important cue for the formation of alliances in stressful conditions

Denial of Reward in the Neonate Shapes Sociability and Serotonergic Activity in the Adult Rat

BACKGROUND: Manipulations of the early environment are linked to long-lasting alterations of emotionality and social capabilities. Denial of rewarding mother-pup interactions in early life of rats could serve as model for child neglect. Negative consequences for social competence in later life, accompanied by changes in the serotonergic system would be expected. In contrast, rewarding mother-pup contact should promote adequate social abilities. METHODOLOGY/PRINCIPAL FINDINGS: Male Wistar rats trained in a T-maze during postnatal days 10-13 under denial (DER) or permission (RER) of maternal contact were tested for play behavior in adolescence and for coping with defeat in adulthood. We estimated serotonin (5-HT) levels in the brain under basal conditions and following defeat, as well as serotonin receptor 1A (5-HT1A) and serotonin transporter (SERT) expression. DER rats exhibited increased aggressive-like play behavior in adolescence (i.e. increased nape attacks, p<0.0001) and selected a proactive coping style during defeat in adulthood (higher sum of proactive behaviors: number of attacks, flights, rearings and defensive upright posture; p = 0.011, p<0.05 vs RER, non-handled-NH). In adulthood, they had lower 5-HT levels in both the prefrontal cortex (p<0.05 vs RER) and the amygdala (p<0.05 vs NH), increased 5-HT levels following defeat (PFC p<0.0001) and decreased serotonin turnover (amygdala p = 0.008). The number of 5-HT1A immunopositive cells in the CA1 hippocampal area was increased (p<0.05 DER, vs RER, NH); SERT levels in the amygdala were elevated (p<0.05 vs RER, NH), but were lower in the prefrontal cortex (p<0.05 vs NH). CONCLUSIONS/SIGNIFICANCE: Denial of expected maternal reward early in life negatively affects sociability and the serotonergic system in a complex manner. We propose that our animal model could contribute to the identification of the neurobiological correlates of early neglect effects on social behavior and coping with challenges, but also in parallel with the effects of a rewarding early-life environment

Memoires van een stressvol bestaan

Het autobiografische geheugen, onze eigen wereld van herinneringen met hoogte- en dieptepunten, dankt zijn inhoud en inkleuring onder andere aan stressvolle ervaringen. Uitdagingen, onverwachte gebeurtenissen, verwachtingen, en hoe we met een situatie omgaan en tot een oplossing komen (of niet), leiden tot de meest heldere herinneringen. Melly Oitzl gaat in haar oratie in op de vraag hoe het komt dat we bepaalde gebeurtenissen beter onthouden dan andere, en ze soms niet kunnen vergeten, ook al zouden we het graag willen. Het antwoord op deze vraag ligt in de stresshormonen, vooral glucocorticoïden, die een centrale rol spelen in de neurobiologie van geheugenprocessen. Oitzl gebruikt de werking van stresshormonen voor translationeel onderzoek naar geheugenprocessen van dier en mens, onder andere door gedetailleerde gedragsanalyse te combineren met de visualisering van hersenprocessen. Haar doel is de mechanismen te ontrafelen die ten grondslag liggen aan de invloed van stress op de hersenen in de verwachting dat dit aanknopingspunten oplevert voor de behandeling van stressgerelateerde ziektes

Stress hormones and post traumatic disorder : basic studies and clinical perspectives /

Includes bibliographical references and index

Stress effects on memory:An update and integration

It is well known that stressful experiences may affect learning and memory processes. Less clear is the exact nature of these stress effects on memory: both enhancing and impairing effects have been reported. These opposite effects may be explained if the different time courses of stress hormone, in particular catecholamine and glucocorticoid, actions are taken into account. Integrating two popular models, we argue here that rapid catecholamine and non-genomic glucocorticoid actions interact in the basolateral amygdala to shift the organism into a 'memory formation mode' that facilitates the consolidation of stressful experiences into long-term memory. The undisturbed consolidation of these experiences is then promoted by genomic glucocorticoid actions that induce a 'memory storage mode', which suppresses competing cognitive processes and thus reduces interference by unrelated material. Highlighting some current trends in the field, we further argue that stress affects learning and memory processes beyond the basolateral amygdala and hippocampus and that stress may pre-program subsequent memory performance when it is experienced during critical periods of brain development

Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory

Activation of central glucocorticoid receptors caused by the stress that is associated with a learning task facilitates storage of the acquired information. The molecular mechanism underlying this phenomenon is entirely unknown. Glucocorticoid receptors can influence transcription both through DNA binding-dependent and -independent mechanisms. To assess the importance of these two modes of action for spatial memory, we here used male mutant mice in which homodimerization and DNA binding of the glucocorticoid receptor is largely prevented (GR(dim/dim)) while protein–protein interactions still can take place. These mice showed a selective impairment of spatial memory in the water maze. Locomotion and anxiety-related parameters measured in an open field and a light/dark preference task were comparable for mutant and control mice. Mutant mice released more corticosterone than control mice under basal resting conditions and in response to swimming, which could have influenced memory processes of the mice. However, mimicking the task-related increase in corticosterone by supplementary injection of corticosterone (250 μg/kg, i.p.) in adrenalectomized mice, resulting in equal plasma corticosterone concentrations in both genotypes, improved spatial memory of control mice but had no effect on mutant mice. These findings suggest that task-related facilitating effects of corticosterone on spatial memory indeed depend on DNA binding of the glucocorticoid receptor rather than on protein–protein interactions of the receptor with other transcription factors. Although it cannot be excluded that both processes are involved in a coordinated way, interrupting the DNA-binding capacity of the receptor is sufficient to induce impairment