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The purpose of this literature review is to summarize stress-related research to better understand the mechanisms of stress. The connections between stress and environmental, physiological, as well as neurological factors were examined. Research has shown that stress exposure was related to cognitive dysfunctions, altered attention strategies, reduced capacity to experience pleasure, and higher risktaking tendency in achieving gains. A high level of stress was associated with greater hippocampal volume loss and was found to hinder memory retrieval while enhancing memory consolidation process. Physiologically, high stress levels were linked to shortened telomeres, elevated levels of circulating inflammatory markers, as well as hypoactivation of electrodermal activity and diurnal cortisol in response to stressors. Moreover, prenatal stress exposure was found to be a risk factor that can make an individual vulnerable to develop later stress-related physical and psychological problems. Researchers have also identified protective factors that can buffer individuals from the negative impact of stress.

The brain of many species including humans, harbors stem cells that continue to generate new neurons up into adulthood. This form of structural plasticity occurs in a limited number of brain regions, i.e. the subventricular zone and the hippocampal dentate gyrus and is regulated by environmental and hormonal factors. In this minireview, we provide an overview of the effects of stress and glucocorticoid hormones on adult hippocampal neurogenesis and discuss how these effects may be relevant for cognitive function and possibly, brain disease. While its exact functional role remains elusive, adult neurogenesis has been implicated in learning and memory, fear and mood regulation and recently, adult-born neurons were found to be involved in specific cognitive functions such as pattern separation (i.e. the ability to form unique memory representations) and cognitive flexibility. The process of adult neurogenesis is influenced by several factors; whereas e.g. exercise stimulates, exposure to stress and stress hormones generally inhibit neurogenesis. Effects of acute, mild stress are generally short-lasting and recover quickly, but chronic or severe forms of stress can induce lasting reductions in adult neurogenesis. Some of the inhibitory effects of stress can be rescued by exercise, by allowing a period of recovery from stress, by drugs that target the stress system, or by some, but not all, antidepressants. Stress may, partly through its effects on adult neurogenesis, alter structure and plasticity of the hippocampal circuit. This can lead to subsequent changes in stress responsivity and aspects of memory processing, which may be particularly relevant for stress related psychopathology or brain diseases that involve perturbed memory processing.

Background Neuroinflammation is considered to be a major factor in several neurodegenerative diseases. Recently, the polyunsaturated fatty acid omega-3 has been shown to have anti-inflammatory effects and might play an effective role in improving memory impairment due to inflammation. In order to test this, we stimulated neuroinflammation in an animal model and induced memory dysfunction as measured by reduced retention of passive avoidance learning (PAL) and altered expression of CaMKII-α , a gene known to be crucial for memory formation. We then investigated whether treatment with dietary omega-3 prevents inflammation-induced memory dysfunction in this model. Methods Male wistar rats (200–220 g) were fed either a control diet or a diet containing omega-3 (400 mg/kg, po) for 1 month prior. Rats then received injection of either saline or LPS (500 μg/kg, ip) and were subjected to the PAL acquisition task. The retention test was performed 24 h later, and animals were sacrificed immediately. Hippocampi were dissected and stored at −80 °C. Finally, TNF-α levels and CaMKII-α gene expression were measured by ELISA and qRT-PCR, respectively. Results We found that LPS treatment significantly impaired PAL and memory, increased TNF-α levels and impaired CaMKII-α gene expression. In control and LPS-injected animals, pre-treatment with omega-3 improved performance on the PAL task and increased CAMKII-α gene expression. Conclusion Taken together, these data suggest that dietary omega-3 may improve cognitive function and provide a potential therapy for memory impairment due to neuroinflammation.

Many studies suggest that glucose can temporarily enhance hippocampal-dependent memories. As the hippocampus plays a key role in associative learning, we examined the influence of glucose on verbal paired associate memory. This study examines how glucose modifies performance on a relational memory task by examining its influence on learning, subsequent forgetting and relearning. A selective reminding procedure was used to show high and low imagability paired associates to 80 participants, who were seen twice. On the first session, they received 25 g glucose pre-learning, 25 g glucose post-learning or placebo. On the second session, 1 week later, they received 25 g glucose or placebo. Cued-recall was evaluated after each learning trial, 1 week later to assess forgetting and after an opportunity to relearn the material forgotten. Glucose did not influence paired associate acquisition. Those given glucose pre-learning tended to forget less material the following week, and independently, glucose at retrieval facilitated cued-recall. Both forms of facilitation were equally apparent on low and high imagability pairs. The benefit of glucose pre-learning was eliminated once the paired associates had been seen again, but the benefit of glucose at retrieval extended into the second relearning trial. The discussion considers the cognitive processes and hippocampal basis for paired associate learning and retention and the implications for glucose’s mode of action. It is proposed that glucose during encoding serves to make the delayed memories initially more available, whereas its influence during delayed retrieval makes available memories temporarily more accessible.

Rationale Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. Objectives We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. Methods This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2Badrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. Results A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-inducedincreases duringrecognition ofemotionalfaces were present in the right hippocampus. Conclusion Thegenotype-dependenteffectsofacutestresson neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

Stress impairs cognition via corticotropin-releasing hormone receptor 1 (CRHR1), but the molecular link between abnormal CRHR1 signaling and stress-induced cognitive impairments remains unclear. We investigated whether the cell adhesion molecule nectin-3 is required for the effects of CRHR1 on cognition and structural remodeling after early-life stress exposure. Postnatally stressed adult mice had decreased hippocampal nectin-3 levels, which could be attenuated by CRHR1 inactivation and mimicked by corticotropin-releasing hormone (CRH) overexpression in forebrain neurons. Acute stress dynamically reduced hippocampal nectin-3 levels, which involved CRH-CRHR1, but not glucocorticoid receptor, signaling. Suppression of hippocampal nectin-3 caused spatial memory deficits and dendritic spine loss, whereas enhancing hippocampal nectin-3 expression rescued the detrimental effects of early-life stress on memory and spine density in adulthood. Our findings suggest that hippocampal nectin-3 is necessary for the effects of stress on memory and structural plasticity and indicate that the CRH-CRHR1 system interacts with the nectin-afadin complex to mediate such effects.

When a consolidated memory is reactivated, it becomes labile and modifiable. Recently, updating of reactivated episodic memory was demonstrated by Hupbach et al. (Learn Mem 14:47–53, 2007). Memory updating involves two vital processes—reactivation followed by reconsolidation. Here, we explored effects of psychosocial stress on episodic memory updating. Based on prior research, we hypothesized that stress before reactivation or stress before reconsolidation would impair memory updating. Participants learned a set of objects (list 1) on day 1. On day 2, some participants were reminded of list 1 before learning a second set of objects (list 2). Memory for list 1 was tested on day 3. Stress was administered either before reactivation of list 1 on day 2 (exp 1) or before reconsolidation of list 1, i.e., after reactivation and learning list 2 on day 2 (exp 2). Memory updating involves the incorporation of list 2 items into list 1 memory, contingent upon the reactivation of list 1 memory. In exp 1, the reminder groups had higher intrusions than the no-reminder groups, but contrary to our predictions, stress did not reduce this reminder effect. Stress effects were, however, found in exp 2: the reminder group that was stressed after reactivation and new learning showed fewer intrusions than the control reminder group. The findings suggest that stress before reactivation does not impair memory updating but stress at the onset of reconsolidation can. Timing may determine the effects of stress on memory processing.

Exposure to severe and prolonged stress has detrimental effects on the hippocampus. However, relatively little is known about the gradual changes in hippocampal structure and its behavioral consequences, over the course of repeated stress. Behavioral analyses during 10 days of chronic stress pointed to a delayed decline in spatial memory, the full impact of which is evident only after the end of stress. In contrast, concurrent volumetric measurements in the same animals revealed significant reduction in hippocampal volumes in stressed animals relative to their unstressed counterparts, as early as the third day of stress. Notably, animals that were behaviorally the worst affected at the end of chronic stress suffered the most pronounced early loss in hippocampal volume. Together, these findings support the view that not only is smaller hippocampal volume linked to stress-induced memory deficits, but it may also act as an early risk factor for the eventual development of cognitive impairments seen in stress-related psychiatric disorders.

Hypothalamic pituitary adrenal (HPA) axis hyperactivity has been linked to learning and memory difficulties in a range of neurodegenerative and neuropsychiatric conditions. In Huntington's disease (HD), both declines in learning and memory and HPA axis dysfunction are present early in the disease. However, the relationship between specific learning and memory deficits and HPA axis functioning in HD has not been examined. The aim of this study was to investigate cortisol levels in relation to verbal learning and memory in pre-diagnosed (pre-HD) participants and patients at the early stages of diagnosed HD (early-HD). Cortisol concentration was assayed in saliva samples from 57 participants (17 early-HD, 20 pre-HD, and 20 controls) at four time-points across a 24-h period. Verbal memory was assessed using the California Verbal Learning Test-Second Edition (CVLT-II). We focused statistical analyses on the late evening cortisol concentration, and examined cortisol levels and verbal memory function in relation to diagnostic group (control, pre-HD, early-HD), and in a separate set of analyses combining pre-HD and early-HD (and excluding controls) we also examined cortisol and verbal memory performance in relation to the severity of HD-related motor signs. Of these two classification approaches, HD motor sign severity was more strongly associated with high evening cortisol levels and both reduced information encoding and memory retrieval. Separately, there was also a trend of higher cortisol levels in pre-HD. The findings suggest hypercortisolism and the underlying pathological changes may begin many years before a clinical diagnosis is made, but the memory decline associated with HPA axis disturbance may only become detectable once motor signs become pronounced.

Memory impairment is a major problem afflicting mankind. The association between memory functions and neurotransmitter functions is of great interest for understanding brain function. Serotonergic pathways play an important role in the modulation of memory functions but the importance of its receptor types and subtypes on memory functions is still unclear. Activation and blockade of various serotonin (5-HT) receptors has been reported to alter cognitive processes and 5-HT receptor antagonism could be beneficial in the treatment of cognitive diseases. The role of 5-HT on memory functions is complicated. Among the 5-HT receptors subtypes, 5-HT(1A) receptors are of special interest because these receptors are present in the brain areas involved in learning and memory functions such as hippocampus and cortex. The present study was therefore designed to investigate the effect of activation and blockade of somatodendritic and/or postsynaptic 5-HT(1A) receptor on learning and memory functions in rats using modified version of water maze. In this study, 8-OH-DPAT (8-hydroxy-2-(di-N-propylamino) tetralin) at 0.3 mg/kg significantly enhanced learning acquisition (LA), short-term memory (STM) and long term memory (LTM) of rats pre-injected with saline suggesting that the activation of pre-synaptic 5-HT(1A) receptors by its agonist enhanced the memory functions of rats. Conversely, rats injected with 8-OH-DPAT at 1.0 mg/kg exhibited impaired LA and STM and had no effect on LTM. It was also shown in this study that blockade of 5-HT(1A) receptors by spiperone enhanced LA, had no effect on STM but impaired the LTM, which showed that the blockade of 5-HT(1A) receptors by its antagonist exerts different effect on different types of memory. This study suggests that 5-HT(1A) receptor could be used as a significant pharmacological target for the treatment of CNS diseases. Unraveling the role of serotonin in cognition and memory disorders could provide better therapy and it may lead to new insights in our understandings of learning and memory.

Corticosteroids, released in high amounts after stress, exert their effects via two different receptors in the brain: glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). GRs have a role in normalizing stress-induced effects and promoting consolidation, while MRs are thought to be important in determining the threshold for activation of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the effects of MR blockade on HPA axis responses to stress and stress-induced changes in cognitive function. In a double-blind, placebo-controlled study, 64 healthy young men received 400 mg of the MR antagonist spironolactone or placebo. After 1.5 h, they were exposed to either a Trier Social Stress Test or a non-stressful control task. Responses to stress were evaluated by hormonal, subjective, and physiological measurements. Afterwards, selective attention, working memory, and long-term memory performance were assessed. Spironolactone increased basal salivary cortisol levels as well as cortisol levels in response to stress. Furthermore, spironolactone significantly impaired selective attention, but only in the control group. The stress group receiving spironolactone showed impaired working memory performance. By contrast, long-term memory was enhanced in this group. These data support a role of MRs in the regulation of the HPA axis under basal conditions as well as in response to stress. The increased availability of cortisol after spironolactone treatment implies enhanced GR activation, which, in combination with MR blockade, presumably resulted in a decreased MR/GR activation ratio. This condition influences both selective attention and performance in various memory tasks. Neuropsychopharmacology (2011) 36, 2720-2728; doi: 10.1038/npp.2011.162; published online 31 August 2011

Item does not contain fulltext It is unknown how antidepressants reverse mood-congruent memory bias, a cognitive core factor causing and maintaining depression. Using a double-blind, placebo-controlled, cross-over design, we investigated the effect of a short-term treatment (14 days) with the dual reuptake inhibitor duloxetine on neural correlates of mood-congruent and mood-incongruent memory formation and retrieval in healthy volunteers who underwent a sad mood induction procedure. Duloxetine did not affect acute mood state or memory performance, but interacted with brain processes mediating mood-congruent memory. It decreased activity related to successful memory formation for mood-congruent and -incongruent items in a set of brain regions comprising the putamen and the middle frontal gyrus, as well as the middle and the anterior cingulate cortex. Duloxetine specifically increased amygdala activity related to successful memory retrieval for mood-incongruent items. Here we show that short-term administration of duloxetine affects the neural correlates of emotional memory formation and retrieval in a set of brain regions whose processing is related to affective state and its regulation. While duloxetine suppressed the neural correlates of emotional memory formation in general, it specifically enhanced amygdala processes associated with mood-incongruent memory retrieval. This pattern of results shows how an antidepressant may reduce emotional memory formation and reverse mood-congruent processing biases at retrieval.

Beneficial effects of St. John's wort (Hypericum perforatum) in the treatment of stress-evoked memory impairment were recently described. In this study, we tested a hypothesis that St. John's wort alleviates stress- and corticosterone-related memory impairments by restoring levels of synaptic plasticity proteins: neuromoduline (GAP-43) and synaptophysin (SYP) in hippocampus and prefrontal cortex. Stressed and corticosterone-treated rats displayed a decline in the acquisition of spatial working memory (p

Interleukin-1β (IL-1β) is one of the first cytokines ever described. It has long been recognized to play an important role in mediating inflammation and orchestrating the physiological and behavioral adjustments that occur during sickness. Recently, accumulating evidence has indicated that IL-1β also adversely affects cognitive function. Nevertheless, there are also some reports showing no effects or even beneficial effects of IL-1β on learning and memory. The relationship between IL-1β and cognitive impairment has not been clearly elucidated. Here we reviewed the evidence of both negative and positive effects of IL-1β on learning and memory, and the key factors that may affect the effects of IL-1β on learning and memory were discussed.

Existing data on the involvement of the hippocampus in contextual memory and the fact that contextual memory is impaired in dreams occurring during paradoxical sleep allowed us to suggest that one of the causes of this impairment consists of changes in the efficiency of synaptic transmission in the hippocampus due to increases (as compared with waking) in the concentrations of acetylcholine, dopamine, and cortisol, as well as the absence of serotonin and noradrenaline. Our previous analysis showed that in paradoxical sleep, long-term depression can be induced all components of the polysynaptic pathway through the hippocampal formation, while potentiation can occur at the inputs from the entorhinal cortex to hippocampal fields CA1 and CA3 and in the associative connections in field CA3. It is hypothesized that the correct functioning of episodic memory requires efficient transmission of signals in each component of the polysynaptic pathway through the hippocampus, allowing a neuronal representation of the context to be created within it. In the state of waking, reproduction of the context of an episode simultaneously activates the neuronal representation of the context remembered in the hippocampus and neuronal representations of the details of the episode remembered in those areas of the cortex in which they were processed. It follows from the proposed mechanism that any neurotransmitter or neuropeptide able to promote longterm potentiation in all components of the polysynaptic pathway through the hippocampus can improve episodic memory. As the consequences of the mechanism are consistent with experimental data, it can be used to seek agents improving episodic memory.

Stress and glucocorticoids (GCs) can facilitate memory formation. However, the molecular mechanisms mediating their effects are largely unknown. alpha-Amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) trafficking has been implicated in the changes in synaptic strength at central glutamatergic synapses associated with memory formation. In cell cultures, corticosterone has been shown to condition the synaptic trafficking of the AMPAR GluA2 subunit. In this study, we investigated the involvement of GluA2 trafficking in the facilitation of learning by stress. Using the water maze spatial task involving different stress levels, mice trained under more stressful conditions (water at 22 degrees C) showed better learning and memory, and higher post-training corticosterone levels, than mice trained under lower stress (water at 30 degrees C). Strikingly, this facilitated learning by stress was accompanied by enhanced synaptic expression of GluA2 AMPARs that was not observed in mice trained under less stressful conditions. Interfering with GC actions by injecting the GC synthesis inhibitor, metyrapone, blocked both the memory facilitation and the enhanced GluA2 trafficking induced by stressful learning. Intracerebroventricular infusion of the peptide, pep2m, that blocks GluA2 synaptic trafficking by interfering with the interaction between N- ethylmaleimide-sensitive factor and GluA2, impaired immediate performance at learning as well as long-term memory retrieval, supporting a causal role for GluA2 trafficking in stress-induced facilitation of spatial learning and memory. Evidence for the involvement of the neural cell adhesion molecule N-cadherin in interaction with GluA2 is also provided. These findings underscore a new mechanism whereby stress can improve memory function.Neuropsychopharmacology advance online publication, 4 November 2009; doi:10.1038/npp.2009.172.

In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

Typically the term "memory" refers to the ability to consciously remember past experiences or previously learned information. This kind of memory is considered to be dependent upon the hippocampal system. However, our emotional state seems to considerably affect the way in which we retain information and the accuracy with which the retention occurs. The amygdala is the most notably involved brain structure in emotional responses and the formation of emotional memories. In this review we describe a system, composed of the amygdala and the hippocampus, that acts synergistically to form long-term memories of significantly emotional events. These brain structures are activated following an emotional event and cross-talk with each other in the process of consolidation. This dual activation of the amygdala and the hippocampus and the dynamics between them may be what gives emotionally based memories their uniqueness.

The effects of systemic administration of thyroid, adrenal cortex, and sex hormones on learning ability, memory trace retention, and behavior were compared in male rats. These studies showed that thyroid, corticosteroid, and sex hormones had no effect on passive learning. Excess quantities of sex hormones disrupted active learning and subsequent reproduction of received information; an excess of thyroid hormone improved the acquisition and retention of the active avoidance habit. Increases in the levels of adrenal cortex hormones worsened active learning and the retention of memory traces, and also increased the level of behavioral activity.

Retrograde amnesia observed following hippocampal lesions in humans and animals is typically temporally graded1,2, with recent memory being impaired while remote memories remain intact, indicating that the hippocampal formation has a time-limited role in memory storage3,4. However, this claim remains controversial because studies involving hippocampal lesions tell us nothing about the contribution of the hippocampus to memory storage if this region was present at the time of memory retrieval5,6. We therefore used non-invasive functional brain imaging using (14C)2-deoxyglucose uptake to examine how the brain circuitry underlying long-term memory storage is reorganized over time in an intact brain. Regional metabolic activity in the brain was mapped in mice tested at different times for retention of a spatial discrimination task. Here we report that increasing the retention interval from 5 days to 25 days resulted in both decreased hippocampal metabolic activity during retention testing and a loss of correlation between hippocampal metabolic activity and memory performance. Concomitantly, a recruitment of certain cortical areas was observed. These results indicate that there is a time-dependent reorganization of the neuronal circuitry underlying long-term memory storage, in which a transitory interaction between the hippocampal formation and the neocortex would mediate the establishment of long-lived cortical memory representations.

Glucocorticoids, a class of steroid hormones, can adversely affect the brain, particularly the hippocampus. The effect is most likely to be indirect and in response to either endogenously or exogenously induced hypercortisolaemia. While the stress response is clearly adaptive and therapeutic doses of synthetic glucocorticoids treat many medical disorders effectively, both corticosterone injections and prolonged stress in rodents can result in changes in glucocorticoid receptor levels, altered hippocampal dendritic morphology, and impaired spatial memory. Less compelling but still provocative is the suggestion that patients with post-traumatic stress disorder or Cushing’s syndrome have decreased hippocampal volume and memory impairment. Of particular clinical relevance is the recent documentation of a memory decline that accompanies standard doses of corticosteroids. Patients with rheumatic disease who received glucocorticoid therapy for at least a year performed worse on memory tasks than closely matched patients with rheumatic disease who were being treated with alternative therapies such as gold. A separate longitudinal study found similar memory declines as early as one week after treatment began. The risk of memory impairment should be carefully considered before initiating treatment with glucocorticoids and their use should be considered in the differential diagnosis of memory loss.

Recent findings have shown that the biochemistry of declarative memory in the areas of the brain involved with its formation and retrieval is strikingly similar to that of long-term potentiation. The memory process, like long-term potentiation, involves a sequence of events that starts by the activation of glutamate receptors, is followed by a variety of enzymatic changes, and involves, some hours after its initiation, gene transcription and protein synthesis. This sequence of events takes place in the hippocampus and, depending on the task, also in amygdala and medial septum and, minutes later, probably in cortical areas of the brain. Peripheral hormones and a variety of brain neuromodulatory systems may enhance or depress different steps of the biochemical sequence. The hormones act in some cases directly on the hippocampus and amygdala (glucocorticoids), and in others (corticotropin, epinephrine) indirectly, through reflex actions on brain neuromodulatory systems (noradrenergic, cholinergic, endorphinergic). The best studied modulatory systems are those related to stress. However, many findings demonstrate a key role in memory modulation of dopaminergic synapses, of brain benzodiazepine-like substances, and perhaps of serotonin acting at specific steps of the biochemistry of memory processes in the hippocampus, amygdala, or elsewhere. Since these systems are involved in the regulation of anxiety and mood, the findings suggest a strong relation between anxiety, mood, and memory, both in normal and in pathological conditions.

The retroactive effects of stress on memory have not received a great deal of empirical attention; however, the research that has been conducted has reported both positive and negative effects of stress on memorial processes. The goal of this study was to examine the effects of a naturalistic Stressor—an intense bout of exercise—on memory for inhibitory fear conditioning in rats. Experiment 1 investigated the retroactive effect of a stressful swim treatment on memory for passive avoidance (PA) training. Rats that received an immediate posttraining swim treatment demonstrated a significant enhancement in performance when tested for retention 24 h later. Furthermore, the enhancing effect of the swim treatment was time dependent: Rats receiving the swim treatment 15 min after PA training no longer exhibited reliably better scores than did rats not receiving the swim treatment. Experiment 2 used preexposures to control for the possibility that the swim treatment was enhancing avoidance scores by acting as a punisher rather than a memory modulator. Results indicate that both the group that was preexposed and the group that was not preexposed showed reliably higher scores than did a group of animals receiving only PA training, thus replicating Experiment 1. Furthermore, the results of Experiment 2 suggest that swimming was not simply acting as a punishing agent, since preexposures to the treatment did not attenuate its memory-enhancing properties. The possible role of stress-related hormones on memory processes is considered.

Memories that can be recalled several hours after learning may paradoxically become inaccessible for brief periods after their formation. This raises major questions about the function of these early memory lapses in the structure of memory consolidation. These questions are difficult to investigate because of the lack of information on the precise timing of lapses. However, the use of a single-trial conditioning paradigm in Lymnaea solves this problem. Here we use electrophysiological and behavioural experiments to reveal lapses in memory recall at 30 min and 2 h post conditioning. We show that only during these lapses is consolidation of long-term memory susceptible to interruption by external disturbance. These shared time points of memory lapse and susceptibility correspond to transitions between different phases of memory that have different molecular requirements. We propose that during periods of molecular transition memory recall is weakened, allowing novel sensory cues to block the consolidation of long-term memory., Memory lapses during memory consolidation are periods when the memory becomes briefly inaccessible after its formation. Marra and colleagues study memory lapses in the mollusc Lymnaea, and find that only during these lapses is consolidation of memories susceptible to interruption by external disturbances.

A top-down pathway from the dorsal anterior cingulate cortex regulates the retrieval of recent fear memories in the hippocampus.

Evidence reviewed here suggests that many treatments that retroactively enhance or impair memory in rats and mice may act by releasing epinephrine from the adrenal medulla: (1) When administered shortly after training, epinephrine injections modulate memory storage processes; (2) plasma epinephrine levels assessed shortly after training predict later performance of learned responses in several situations; and furthermore, (3) peripherally administered adrenergic antagonists block the effects on memory of epinephrine and of many other treatments that enhance and impair memory. In addition, the rapid forgetting exhibited by juvenile and aged rodents can be retarded (i.e., memory is improved) by posttraining epinephrine injections, suggesting that age-related memory deficits may reflect inadequate functions of those neuroendocrine systems responsible, in part, for regulating memory storage. These results, together with the additional finding that epinephrine enhances the establishment of a neurophysiological analogue of memory, long-term potentiation, suggest that the hormone regulates neurobiological processes responsible for memory formation.

Verbal learning was measured during the administration of l-DOPA in large oral doses to depressed patients. Longer-term memory on two different tasks improved during treatment, while short-term memory (immediate recall) was unaffected. In contrast, the catecholamine synthesis inhibitor α-methyl-p-tyrosine did not alter either memory process.