Stress is something that every individual must deal with on a day to day basis. Although stress influences a number of our bodily functions, one key impact it has is on our memory. Although many studies have been performed to suggest memory is impaired by stress, it is not so clear cut. Important factors that mediate the effects of stress on memory is the type of stress being induced and the emotional saliency of the stimuli. The stage in which stress is being experienced is also important, as it has been found that stress enhances consolidation, impairs retrieval and has both positive and negative effects when implicated with the encoding stage . Glucocorticoids, especially cortisol, have been implicated in the effects of stress on memory. Different regions of the brain are also involved in stress and cognition, such as the hippocampus, amygdala  and prefrontal cortex . The interactions between such regions during different stages of memory help understand the mechanism involved. One specific mechanism that has been investigated is the CaMKIIα-BDNF-CREB pathways  which have been found to be the underlying mechanism for the positive effects of stress on consolidation.
|Stress and its influence on memory 
Table of Contents
1 Short Term Memory
1.1 Working Memory
1.1.1 Animal Models
Spatial working memory of rodents is impaired by stress. Inducing chronic stress by means of water baths every day for four weeks, spatial working memory was tested using the T-maze task after a delay. Impairments of spatial working memory are portrayed by a decrease in T-maze accuracy as well as prolongued duration of task performance. Other tasks, such as the Y-maze have shown similar results. Chronic restrained stress results in impaired spatial working memory, evident by the fewer number of times rats enter novel arms relative to the controls, as well as a reduction in time spent exploring the novel arms .
It has been noticed that there is a sex difference in the impairments of spatial working memory induced by stress for rodents. Chronic stress caused by restraint was seen to have negative effects of spatial working memory for both male and female rats within the first minute or two of their Y-maze performance. Despite both males and females showing impairments, after a few minutes the females show improvements and regain their spatial working memory, shown by their increased curiosity to enter novel arms and time spent in them. This is not seen in male rats, as they show continued impairment. This temporary deficit in spatial working memory has been seen when female rats are exposed to chronic stress. These findings suggest that acute stress facilitates spatial working memory, however only for female rats. Despite only males presenting with impairments, corticosterone levels of stressed males and females are high and equal, thus implicating the female estrous cycle playing a role.
|Reaction times for stressed and control
participants during target-present trials and
target-absent trials. 
There have been some studies investigating the effects of stress on working memory in humans, however not all the findings are in line with one another. Using the cold pressor stress test test (CPS), stress was induced and the Sternberg task was used to assess working memory. The Sternberg task involves showing participants 1-4 letters on a screen during the training phase, and after a delay, 2-4 letters are shown. Working memory is tested by how fast and accurate participants are at detecting whether a target item is present or not. The number of letters shown during the training and testing phase allow for different cognitive loads (the more letters, the higher the load). It was found that the acute stress has both enhancing and impairing effects. During high cognitive load, participants had faster reaction times in target-present and target-absent screens (Figure 2), yet their accuracy was lower than the control. Stressed participants were more likely to have false recognitions during target-absent phases, when cognitive load was high.
Psychosocial stress effects working memory in a negative manner. Performance on Sternberg’s delayed recognition tasks show that psychosocial stress result in greater number of errors made during present-target trials than absent-target trials, which was more significant when there was high cognitive load. These differing findings of the effect of stress on working memory suggest that the degree(change) of detriment depends on the type of stress being experienced. The increased adrenergic activity associated with psychosocial stress has been linked to impairments in working memory.
1.1.3 Prefrontal Cortex
The role of dopamine and the prefrontal cortex (PFC) has been related to numerous neuropsychiatric disorders involving impairments in working memory. Findings of Mizoguchi et al. suggest that these impairments are a result of a hypodopaminergic mechanism in the PFC. Rats were subjected to stress for a period of four weeks, and then given a recovery period of 10 days. The T-maze was used to administer a delayed-alternation task in order to test their working memory. This was followed by injection of a D1 receptor agonist, SKF 81297 bilaterally for some rats, whereas others had no injection or were injected with D1 receptor antagonist, SCH 23390. Behaviours of the rats were tested after injections. The rats that were exposed to chronic stress had impaired working memory, which was reversed by the D1 receptor agonist. Chronically stressed rats showed a reduction in DA transmission and upregulation of D1 receptors in the PFC. These findings elucidate the role of the PFC in stress and its impairments towards working memory, functioning through a hypodopaminergic mechanism.
2 Long Term Memory
Long term memory is composed of different stages: encoding, consolidation, retrieval as well as reconsolidation. The influence of stress on long term memory depends on what stage stress is being experienced or induced. Stress has an enhancing effect when experienced during the consolidation and encoding phase, however during retrieval and reconsolidation stress poses a negative influence. Despite these relationships having been found between stress and its influences on the different stages, other factors such as emotional arousal and saliency of the cue play a role in determining whether stress augments or diminishes memory.
The quality of one’s memory relies on the encoding phase. There have been enhancements in memory when there is a level of stress being experienced. Studies have found that there is an interaction between the stress hormones and level of arousal associated with the stimuli, yet there is inconsistency as to when stress should be induced in order to have optimal enhancement.
|Mean scores of free memory recall for all three groups.
Individuals of the stressed group had greater free recall for words/
when there was context-congruency between stress and words. 
Stress induced prior to encoding has been found to have enhancing effects. A study conducted by Payne et al. in 2007 investigated this notion by giving participants the Trier Social Stress Test (TSST) or no stress. Immediately after, emotional and neutral images were presented. One week later, participants were called back to have their memory tested. It was found that free recall for emotional images was better for those who were exposed to TSST, yet no effect was seen with neutral images (Figure 3). Cued recall tasks provided the same results. However, it was seen that stress prior to encoding may have a detrimental effect on memory for neutral stimuli, evident by the greater occurrence of false memories experienced by the stressed participants. This study suggests that pre-encoding stress has its benefits, which are manifested through improved memory recall for emotional stimuli, yet recall for neutral stimuli may be impaired. Other studies have investigated emotional arousal and emotional valence interacting with exogenous cortisol prior to encoding, and there was an interaction between greater cortisol levels and memory for images associated with greater arousal. No such interaction was found between cortisol levels and emotional valence.
2.1.2 During Encoding
Testing to see whether stress influences memory, some studies have induced stress during the time of encoding. Smeets et al. were looking to test whether context-congruency plays a role in memory, and in doing so they administered stress during the encoding phase. Participants were exposed to personality stress, memory stress—both through the TSST—or no stress at all. This exposure was in time with the reading of words associated to the type of stress, ie. personality stress participants were presented with words such as anxious, neurotic; memory stress participants heard words such as knowledge. It was found that individuals who were presented with personality stress and personality words had greater memory recall, yet this was not seen for individuals of no stress or even memory stress. This could be because in the personality stress condition and words, certain words could have caused a threat to ego, potentially resulting in more attention being paid to these words. The findings of Smeets et al. suggest that stress does have an enhancing effect on memory when presented during the encoding phase, however only for personality context-congruency.
|Accuracy of image recall. Stressed participants had greater accuracy
for emotional stimuli, whereas no enhancements were seen for neutral stimuli.
Stress induced after encoding has also been investigated. Individuals who were exposed to stress after encoding had greater memory for emotional images than neutral ones and more details were recalled (Figure 4). There was no significant difference for memory of neutral stimuli between the stressed and control groups (Figure 4). The increase in salivary cortisol levels after the induction of stress suggests this increase interacts with the level of emotion associated with the stimuli such that the stronger associations are related to greater memory recall.
Despite studies exposing participants to stress at different times of encoding, their findings provide evidence that emotional arousal associated with the stimuli is key for enhanced memory, and also suggests that there is an even stronger effect when there is context-congruency. Neutral stimuli may be most influenced by the time of stress being induced, as those induced prior to encoding experience impaired memory recall, exemplified through false memory recalls, whereas during or after encoding there are no enhancements or impairments.
2.2.1 CaMKIIα-BDNF-CREB pathways
The role of glucocorticoids have been suggested to play a role in memory consolidation. An inverted U-shape relationship between glucocorticoids, primarily cortisol, and memory consolidation exists. With the use of CPS and a delayed recall of a story, the quadratic relationship between cortisol and memory consolidation was investigated. It was found that there was a quadratic relationship between cortisol levels in the saliva and correct recall. This inverted U-shape relationship indicates that too little stress shows no improvement for consolidation, whereas too much is impairing. For optimal memory consolidation, mid-range levels are best.
Although this relationship has been implicated in many studies, the underlying mechanism for memory consolidation remains unclear. A study conducted by Chen et al. in 2012 has suggested that glucocorticoids mediate memory consolidation through the recruitment of the CaMKIIα –BDNF-CREB pathways. The different pathways which are activated by glucocorticoid receptors in the hippocampus were investigated through the use of naïve rats, vehicles and RU486—a glucocorticoid antagonist. Inhibitory avoidance learning tasks were administered to rats, where foot shocks of varying strengths were given. Injection of RU428 or the vehicle was given 15 minutes before the training, and then 30 minutes or 20 hours after learning their brains were investigated. The phosphorylation of proteins involved in long-term plasticity, such as CaMKIIα, ERK1/2, Akt, phospholipase Cγ (PCγ), mitogen and stress-activated kinase 1 (MSK1), Synapsin-1 and CREB. It was found that after 30 minutes and 20 hours, there was an increase in phosphorylated CREB, Arc and CaMKIIα in the vehicle yet these effects were blocked with RU428 administration. RU428 administration also decreased the phosphorylation of ERK, Akt and PLCγ, which are activated by BDNF. BDNF receptors, TrkB, decreased in phosphorylation in RU428 mice. Since RU428 is a glucocorticoid receptor antagonist, it was evident through the vehicle mice that glugocorticoids utilize these synaptic plasticity pathways.
2.2.2 Insular Cortex
The insular cortex has been implicated in mediating the effects of glucocorticoids on emotional memory consolidation. The insular cortex is involved in fear memories and mediating the effects of gluocorticoids in memory consolidation for emotional memories. A study conducted by Fornari et al. in 2011 used emotionally arousing inhibitory avoidance training with rats. Glucocorticoid agonist RU28362 was infused bilaterally into the insular cortex after one training session and it was found that retention increased after 48 hours. This increase of retention was seen to be associated with the increase in ERK1/2 phosphorylation, which is important for memory consolidation. Administering corticosterones was found to reduce phosphorylated ERK1/2 in the insular cortex. These findings along with findings of the insular cortex being involved in emotional memories suggest that there is stronger consolidation of emotional memories due to increased insular activity resulting in the expression of phosphorylated ERK1/2 aiding with consolidation.
2.2.3 Hippocampus and Amygdala
The hippocampus is a region of the brain involved in memory retrieval and glucocorticoid receptor acitivty in the hippocampus is linked to retrieval impairments. Propranolol, a ß-adrenoreceptor antagonist, has been used to suggest that improved recall of emotional stimuli may be due to the hippocampus and amygdala being activated in parallel, whereas neutral stimuli does not cause the activation of the amygdala. Administration of propranolol reversed these impairements in memory retrieval. Other studies have pinpointed the basolateral complex of the amygdala (BLA) to be the key brain region, which has been found to be interactive with the hippocampus, such that the BLA mediates the negative hippocampal influence of retrieval through ß-adrenergic activity. This has been found through the use of glucocorticoid receptor agonist RU28362. By injecting the agonist into the hippocampus, memory retrieval of rats was impaired, indicated by more time spent in the wrong quadrants during the water maze (Video 1) task. Again, the administration of propranolol in the BLA blocks these impairments, providing evidence of the BLA mediating the negative influence of hippocampus on memory retrieval.
|Rat performing the Morris Water Maze—
a task used to test for spatial working memory. 
|Rodent performing the object recognition task. |
Stress has been correlated to poor memory retrieval. High levels of glucocorticoids associated with stress is associated with impairment in memory retrieval, seen in both humans and rodents. Rats show impairments through their performance on object recognition tasks (Video 2) and object location tasks. Compared to controls, they spend more time with the familiar object as opposed to the novel one, and they spend more time in the familiar location instead of novel location. Higher plasma corticosterone was negatively correlated with memory retrieval.
Increased cortisol response has been found to cause impairments. However there are conflicting findings of whether a mild stress with no cortisol response leads to enhancements of memory retrieval. Whereas some show no improvements and no impairments, superior memory retrieval has been seen with people who experience stress but no cortisol response.
Reconsolidation is the process of reactivating memories that have been consolidated, and placing them into a sensitive state where they are able to change.
Human and animal studies have been consistent in investigating how stress influences reconsolidation. Reconsolidation in humans is impaired when exposed to arousal, however this is seen only with neutral memories. Rat studies have found that reconsolidation is not always impaired when exposed to a stressor . Maroun et al. investigated the influence of arousal and stress on memory consolidation and reconsolidation. Rats who had high arousal showed impaired memory consolidation, however reconsolidation was enhanced. This was not seen in rats who had been habituated and had little arousal, portrayed by their impairments in both consolidation and reconsolidation. These findings suggest that the influence of stress on reconsolidation is dependent on the level of arousal being experienced at the time.