Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis

It is well known that adult neurogenesis occurs in two distinct regions, the subgranular zone of the dentate gyrus and the subventricular zone along the walls of the lateral ventricles. Until now, the contribution of these newly born neurons to behavior and cognition is still uncertain. The current study tested the functional impacts of diminished hippocampal neurogenesis on emotional and cognitive functions in transgenic Gfap‐tk mice. Our results showed that anxiety‐related behavior evaluated both in the elevated plus maze as well as in the open field, social interaction in the sociability test, and spatial working memory in the spontaneous alternation test were not affected. On the other hand, recognition and emotional memory in the object recognition test and contextual fear conditioning, and hippocampal long‐term potentiation were impaired in transgenic mice. Furthermore, we evaluated whether environmental enrichment together with physical exercise could improve or even restore the level of adult neurogenesis, as well as the behavioral functions. Our results clearly demonstrated that environmental enrichment together with physical exercise successfully elevated the overall number of progenitor cells and young neurons in the dentate gyrus of transgenic mice. Furthermore, it led to a significant improvement in object recognition memory and contextual fear conditioning, and reverted impairments in hippocampal long‐term potentiation. Thus, our results confirm the importance of adult neurogenesis for learning and memory processes and for hippocampal circuitry in general. Environmental enrichment and physical exercise beneficially influenced adult neurogenesis after it had been disrupted and most importantly recovered cognitive functions and long‐term potentiation. © 2016 Wiley Periodicals, Inc.     

Enriched environment restores hippocampal cell proliferation and ameliorates cognitive deficits in chronically stressed rats

Adult neurogenesis, particularly in the subgranular zone, is thought to be linked with learning and memory. Chronic stress inhibits adult hippocampal neurogenesis and also impairs learning and memory. On the other hand, exposure to enriched environment (EE) is reported to enhance the survival of new neurons and improve cognition. Accordingly, in the present study, we examined whether short‐term EE after stress could ameliorate the stress‐induced decrease in hippocampal cell proliferation and impairment in radial arm maze learning. After restraint stress (6 hr/day, 21 days) adult rats were exposed to EE (6 hr/day, 10 days). We observed that chronic restraint stress severely affected formation of new cells and learning. Stressed rats showed a significant decrease (70%) in the number of BrdU (5‐bromo‐2′‐deoxyuridine)‐immunoreactive cells and impairment in the performance of the partially baited radial arm maze task. Interestingly, EE after stress completely restored the hippocampal cell proliferation. On par with the restoration of hippocampal cytogenesis, short‐term EE after stress resulted in a significant increase in percentage correct choices and a decrease in the number of reference memory errors compared with the stressed animals. Also, EE per se significantly increased the cell proliferation compared with controls. Furthermore, stress significantly reduced the hippocampal volume that was reversed after EE. Our observations demonstrate that short‐term EE completely ameliorates the stress‐induced decrease in cell proliferation and learning deficit, thus demonstrating the efficiency of rehabilitation in reversal of stress‐induced deficits and suggesting a probable role of newly formed cells in the effects of EE. © 2008 Wiley‐Liss, Inc.     

Chemotherapy disrupts learning,neurogenesis and theta activity in the adult brain

Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood–brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3–12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague–Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta‐band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the ‘chemobrain’.     

Targeting hippocampal adult neurogenesis using transcription factors to reduce Alzheimer's disease‐associated memory impairments

Hippocampal adult neurogenesis results in the persisting formation of new neurons that contribute to hippocampal‐dependent learning and memory. This has led to the hypothesis that memory impairments associated with neurodegenerative diseases such as Alzheimer's disease may involve abnormal neurogenesis. Supporting this idea, evidence for decreased adult neurogenesis has been reported in the brain of Alzheimer's disease patients and in several mouse models of the disease. Thus, the development of strategies designed to stimulate the production of new neurons in the diseased brain has raised growing interest. In this review, we discuss putative strategies and present recent studies showing that it is now possible to instruct hippocampal endogenous neural progenitors to adopt an exclusive neuronal fate. We further report how such strategies lead to the rescue of cognitive functions in mouse models of Alzheimer's disease. Altogether, these findings provide the proof‐of‐concept that neurogenesis can be stimulated in the adult brain in vivo, and consequently overcomes pathological memory deficits.     

NADPH oxidase mediates β-amyloid peptide-induced activation of ERK in hippocampal organotypic cultures

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.     

Age‐dependent effects of hippocampal neurogenesis suppression on spatial learning

Reducing hippocampal neurogenesis sometimes, but not always, disrupts hippocampus‐dependent learning and memory. Here, we tested whether animal age, which regulates rate of hippocampal neurogenesis, is a factor that influences whether deficits in spatial learning are observed after reduction of neurogenesis. We found that suppressing the generation of new hippocampal neurons via treatment with temozolomide, an antiproliferation agent, impaired learning the location of a hidden platform in the water maze in juvenile mice (1–2 months old) but not in adult mice (2–3 months old) or middle‐aged mice (11–12 months old). These findings suggest that during juvenility, suppression of neurogenesis may alter hippocampal development, whereas during adulthood and aging, pre‐existing neurons may compensate for the lack of new hippocampal neurons. © 2012 Wiley Periodicals, Inc.     

Time‐dependent enhancement of hippocampus‐dependent memory after treatment with memantine: Implications for enhanced hippocampal adult neurogenesis

Adult hippocampal neurogenesis has been suggested to play modulatory roles in learning and memory. Importantly, previous studies have shown that newborn neurons in the adult hippocampus are integrated into the dentate gyrus circuit and are recruited more efficiently into the hippocampal memory trace of mice when they become 3 weeks old. Interestingly, a single high‐dose treatment with the N‐methyl‐d ‐aspartate receptor antagonist memantine (MEM) has been shown to increase hippocampal neurogenesis dramatically by promoting cell proliferation. In the present study, to understand the impact of increased adult neurogenesis on memory performance, we examined the effects of a single treatment of MEM on hippocampus‐dependent memory in mice. Interestingly, mice treated with MEM showed an improvement of hippocampus‐dependent spatial and social recognition memories when they were trained and tested at 3–6 weeks, but not at 3 days or 4 months, after treatment with MEM. Importantly, we observed a significant positive correlation between the scores for spatial memory (probe trial in the Morris water maze task) and the number of young mature neurons (3 weeks old) in MEM‐treated mice, but not saline‐treated mice. We also observed that the young mature neurons generated by treatment with MEM were recruited into the trace of spatial memory similarly to those generated through endogenous neurogenesis. Taken together, our observations suggest that treatment with MEM temporally improves hippocampus‐dependent memory formation and that the newborn neurons increased by treatment with MEM contribute to this improvement when they become 3 weeks old. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Sexual experience restores age‐related decline in adult neurogenesis and hippocampal function

Aging is associated with compromised hippocampal function and reduced adult neurogenesis in the dentate gyrus. As new neurons have been linked to hippocampal functions, such as cognition, age‐related decline in new neuron formation may contribute to impaired hippocampal function. We investigated whether a rewarding experience known to stimulate neurogenesis in young adult rats, namely sexual experience, would restore new neuron production and hippocampal function in middle‐aged rats. Sexual experience enhanced the number of newly generated neurons in the dentate gyrus with both single and repeated exposures in middle‐aged rats. Following continuous long‐term exposure to sexual experience, cognitive function was improved. However, when a prolonged withdrawal period was introduced between the final mating experience and behavioral testing, the improvements in cognitive function were lost despite the presence of more new neurons. Taken together, these results suggest that repeated sexual experience can stimulate adult neurogenesis and restore cognitive function in the middle‐aged rat as long as the experience persists throughout the testing period. The extent to which changes in adult neurogenesis underlie those in cognition remain unknown. © 2013 Wiley Periodicals, Inc.     

Neurogenesis within the adult hippocampus under physiological conditions and in depression

Adult neurogenesis can only be observed in some specific brain regions. One of these areas is the dentate gyrus of the hippocampal formation. The progenitor cells located in the subgranular layer of the dentate gyrus proliferate, differentiate, and give rise to young neurons that can become integrated into existing neuronal circuits. Under physiological conditions, hippocampal neurogenesis is linked to hippocampal-dependent learning, whereas deficits in adult hippocampal neurogenesis have been shown to correlate with disturbances in spatial learning and memory. This review summarizes the phenomenon of adult hippocampal neurogenesis and the use of suitable markers for the investigation of adult hippocampal neurogenesis. In addition, we focused on the disturbances in neurogenesis that can be seen in depression. Interestingly, several antidepressants have been found to be capable of increasing the rate of hippocampal neurogenesis. Based on that, it can be speculated that factors, which directly or indirectly increase the rate of hippocampal neurogenesis, may be helpful in the treatment of depression.     

Functional consequences of stress-related suppression of adult hippocampal neurogenesis - a novel hypothesis on the neurobiology of burnout

BACKGROUND: Burnout is generally recognized as a work-related stress-induced condition associated with memory problems, fatigue, a sense of inadequacy, and depressed mood. Neurogenesis, the formation of new neurons in the human adult brain, provides a newly discovered dimension of brain plasticity. OBJECTIVES: In a novel theory, we propose that the failure of adult hippocampal neurogenesis may provide the biological and cellular basis for altered brain plasticity in stress-related syndromes like burnout. METHODS: A number of recent animal studies have shown that the rate of neurogenesis in the adult hippocampus may provide an important neurobiological correlate to the symptoms of stress. RESULTS: As of yet, the normal physiological function of new neurons in the adult hippocampus remains unresolved although a number of studies and reviews indicate the importance of neurogenesis for memory and learning. CONCLUSION: In line with this hypothesis, we propose burnout to be an exponent of stress-mediated decrease in adult neurogenesis leading to a decreased ability to cope with stress through decreased hippocampal function possibly involving a disturbed hippocampal regulation of the hypothalamo-pituitary-adrenal axis (HPA axis).     

Irradiation as an experimental tool in studies of adult neurogenesis

"Loss of function" experiments have been the mainstay approach in studies seeking to determine functional roles of various brain regions in learning and memory. The hippocampal formation consists of several distinct regions that are thought to play different, yet interrelated, roles in the memory processes. Ionizing radiation offers a selective and highly flexible, relatively uninvasive method to further advance such studies. Focused applications of the radiation beam to the head under general anesthesia can selectively reduce ongoing adult neurogenesis in the dentate gyrus without causing any detectable damage to mature neurons. Further refinements of the methodology should offer many opportunities to extend our present knowledge of how and when adult neurogenesis plays a role in learning and memory.     

New neurons in the adult brain: the role of sleep and consequences of sleep loss

Research over the last few decades has firmly established that new neurons are generated in selected areas of the adult mammalian brain, particularly the dentate gyrus of the hippocampal formation and the subventricular zone of the lateral ventricles. The function of adult-born neurons is still a matter of debate. In the case of the hippocampus, integration of new cells in to the existing neuronal circuitry may be involved in memory processes and the regulation of emotionality. In recent years, various studies have examined how the production of new cells and their development into neurons is affected by sleep and sleep loss. While disruption of sleep for a period shorter than one day appears to have little effect on the basal rate of cell proliferation, prolonged restriction or disruption of sleep may have cumulative effects leading to a major decrease in hippocampal cell proliferation, cell survival and neurogenesis. Importantly, while short sleep deprivation may not affect the basal rate of cell proliferation, one study in rats shows that even mild sleep restriction may interfere with the increase in neurogenesis that normally occurs with hippocampus-dependent learning. Since sleep deprivation also disturbs memory formation, these data suggest that promoting survival, maturation and integration of new cells may be an unexplored mechanism by which sleep supports learning and memory processes. Most methods of sleep deprivation that have been employed affect both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Available data favor the hypothesis that decreases in cell proliferation are related to a reduction in REM sleep, whereas decreases in the number of cells that subsequently develop into adult neurons may be related to reductions in both NREM and REM sleep. The mechanisms by which sleep loss affects different aspects of adult neurogenesis are unknown. It has been proposed that adverse effects of sleep disruption may be mediated by stress and glucocorticoids. However, a number of studies clearly show that prolonged sleep loss can inhibit hippocampal neurogenesis independent of adrenal stress hormones. In conclusion, while modest sleep restriction may interfere with the enhancement of neurogenesis associated with learning processes, prolonged sleep disruption may even affect the basal rates of cell proliferation and neurogenesis. These effects of sleep loss may endanger hippocampal integrity, thereby leading to cognitive dysfunction and contributing to the development of mood disorders.     

When is adult hippocampal neurogenesis necessary for learning? evidence from animal research

The hippocampus is a key brain structure involved in the short- and long-term processing of declarative memory. Since adult hippocampal neurogenesis was first found, numerous studies have tried to establish the contribution of newborn neurons to hippocampus-dependent cognitive functions. However, this large amount of research has generated contradictory results. In this paper, we review the body of evidence investigating the relationship between hippocampal neurogenesis and learning to conclude the functional role of adult-born hippocampal neurons. First, factors that could explain discrepancies among experiments are taken into account. Then, in addition to methodological differences, we emphasize the importance of the age of the newborn neurons studied, as to how their maturation influences both their properties and potential functionality. Next, we discuss which declarative memory components could require involvement of adult hippocampal neurogenesis, taking into consideration the representational demands of the task, its difficulty and the level of performance reached by the subject. Finally, other factors that could modulate neurogenesis and memory, such as stress levels or previous experience of the animal, should also be taken into consideration in interpreting experiments focused on neurogenesis. In conclusion, our analysis of published studies suggests that new adult-born neurons, under certain circumstances, have a crucial and irreplaceable role in hippocampal learning.     

Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory

Although there is evidence suggesting that adult neurogenesis may contribute to hippocampus-dependent memory, signaling mechanisms responsible for adult hippocampal neurogenesis are not well characterized. Here we report that ERK5 mitogen-activated protein kinase is specifically expressed in the neurogenic regions of the adult mouse brain. The inducible and conditional knock-out (icKO) of erk5 specifically in neural progenitors of the adult mouse brain attenuated adult hippocampal neurogenesis. It also caused deficits in several forms of hippocampus-dependent memory, including contextual fear conditioning generated by a weak footshock. The ERK5 icKO mice were also deficient in contextual fear extinction and reversal of Morris water maze spatial learning and memory, suggesting that adult neurogenesis plays an important role in hippocampus-dependent learning flexibility. Furthermore, our data suggest a critical role for ERK5-mediated adult neurogenesis in pattern separation, a form of dentate gyrus-dependent spatial learning and memory. Moreover, ERK5 icKO mice have no memory 21 d after training in the passive avoidance test, suggesting a pivotal role for adult hippocampal neurogenesis in the expression of remote memory. Together, our results implicate ERK5 as a novel signaling molecule regulating adult neurogenesis and provide strong evidence that adult neurogenesis is critical for several forms of hippocampus-dependent memory formation, including fear extinction, and for the expression of remote memory.     

Hippocampus‐dependent learning is associated with adult neurogenesis in MRL/MpJ mice

The hippocampus is involved in declarative memory and produces new neurons throughout adulthood. Numerous experiments have been aimed at testing the possibility that adult neurogenesis is required for learning and memory. However, progress has been encumbered by the fact that abating adult neurogenesis usually affects other biological processes, confounding the interpretation of such experiments. In an effort to circumvent this problem, we used a reverse approach to test the role of neurogenesis in hippocampus‐dependent learning, exploiting the low levels of adult neurogenesis in the MRL/MpJ strain of mice compared with other mouse strains. We observed that adult MRL/MpJ mice produce 75% fewer new neurons in the dentate gyrus than age‐matched C57BL/6 mice. Learning‐induced synaptic remodeling, spatial learning, and visual recognition learning were reduced in MRL/MpJ mice compared with C57BL/6 mice. When MRL/MpJ mice were allowed unlimited access to running wheels, neurogenesis along with spatial learning and visual recognition learning were increased to levels comparable to those in running C57BL/6 mice. Together, these results suggest that adult neurogenesis is correlated with spatial learning and visual recognition learning, possibly by modulating morphological plasticity in the dentate gyrus. © 2009 Wiley‐Liss, Inc.     

Genetic deletion of melanin‐concentrating hormone neurons impairs hippocampal short‐term synaptic plasticity and hippocampal‐dependent forms of short‐term memory

The cognitive role of melanin‐concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero‐lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long‐term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal‐dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long‐term potentiation and depression in the CA1 area of the hippocampus. Post‐tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre‐synaptic forms of short‐term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short‐term memory T‐maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short‐term memory by impairing short‐term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short‐term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.     

The effects of running and of inhibiting adult neurogenesis on learning and memory in rats

The presence of ongoing adult neurogenesis within the highly plastic hippocampal circuitry poses questions as to the relevance of new neurons to learning and memory. Correlational and causal evidence suggests that some, but not all, hippocampal tasks involve the new neurons. The evidence with regard to spatial learning in the water maze, one of the most commonly used hippocampal tasks, is contradictory. In this study we examined the effects of irradiation-induced reduction in neurogenesis on spatial learning and another standard hippocampal task, contextual fear conditioning, in rats that experienced normal cage conditions or voluntary running. The results indicate that reduced neurogenesis had little effect on spatial learning but severely impaired contextual fear conditioning. It was suggested that compensatory mechanisms within the hippocampus may have contributed selectively to sparing of spatial function. Performance on the fear conditioning task was weakly related to enhanced neurogenesis or running. The results improve our understanding of the functional role of adult neurogenesis in behaving animals.     

Effect of electroconvulsive seizures on pattern separation

Strategies employing different techniques to inhibit or stimulate neurogenesis have implicated a role for adult‐born neurons in the therapeutic effect of antidepressant drugs, as well as a role in memory formation. Electroconvulsive seizures (ECS), an animal model of electroconvulsive therapy, robustly stimulate hippocampal neurogenesis, but it is not known how this relates to either therapeutic efficacy or unwanted cognitive side effects. We hypothesized that the ECS‐derived increase in adult‐born neurons would manifest in improved pattern separation ability, a memory function that is believed to be both hippocampus‐dependent and coupled to neurogenesis. To test this hypothesis, we stimulated neurogenesis in adult rats by treating them with a series of ECS and compared their performances in a trial‐unique delayed nonmatching‐to‐location task (TUNL) to a control group. TUNL performance was analyzed over a 12‐week period, during which newly formed neurons differentiate and become functionally integrated in the hippocampal neurocircuitry. Task difficulty was manipulated by modifying the delay between sample and choice, and by varying the spatial similarity between target and distracter location. Although animals learned the task and improved the number of correct responses over time, ECS did not influence spatial pattern separation ability. © 2015 Wiley Periodicals, Inc.     

Posttraining ablation of adult-generated neurons degrades previously acquired memories

New neurons are continuously generated in the subgranular zone of the adult hippocampus and, once sufficiently mature, are thought to integrate into hippocampal memory circuits. However, whether they play an essential role in subsequent memory expression is not known. Previous studies have shown that suppression of adult neurogenesis often (but not always) impairs subsequent hippocampus-dependent learning (i.e., produces anterograde effects). A major challenge for these studies is that these new neurons represent only a small subpopulation of all dentate granule cells, and so there is large potential for either partial or complete compensation by granule cells generated earlier on during development. A potentially more powerful approach to investigate this question would be to ablate adult-generated neurons after they have already become part of a memory trace (i.e., retrograde effects). Here we developed a diphtheria toxin-based strategy in mice that allowed us to selectively ablate a population of predominantly mature, adult-generated neurons either before or after learning, without affecting ongoing neurogenesis. Removal of these neurons before learning did not prevent the formation of new contextual fear or water maze memories. In contrast, removal of an equivalent population after learning degraded existing contextual fear and water maze memories, without affecting nonhippocampal memory. Ablation of these adult-generated neurons even 1 month after learning produced equivalent memory degradation in the water maze. These retrograde effects suggest that adult-generated neurons form a critical and enduring component of hippocampal memory traces.     

Chronic early life stress alters developmental and adult neurogenesis and impairs cognitive function in mice

Early life stress (ES) increases vulnerability to psychopathology and impairs cognition in adulthood. These ES‐induced deficits are associated with lasting changes in hippocampal plasticity. Detailed information on the neurobiological basis, the onset, and progression of such changes and their sex‐specificity is currently lacking but is required to tailor specific intervention strategies. Here, we use a chronic ES mouse model based on limited nesting and bedding material from postnatal day (P) 2–9 to investigate; (1) if ES leads to impairments in hippocampus‐dependent cognitive function in adulthood and (2) if these alterations are paralleled by changes in developmental and/or adult hippocampal neurogenesis. ES increased developmental neurogenesis (proliferation and differentiation) in the dentate gyrus (DG) at P9, and the number of immature (NeurD1⁺) cells migrating postnatally from the secondary dentate matrix, indicating prompt changes in DG structure in both sexes. ES lastingly reduced DG volume and the long‐term survival of developmentally born neurons in both sexes at P150. In adult male mice only, ES reduced survival of adult‐born neurons (BrdU/NeuN⁺ cells), while proliferation (Ki67⁺) and differentiation (DCX⁺) were unaffected. These changes correlated with impaired performance in all learning and memory tasks used here. In contrast, in female mice, despite early alterations in developmental neurogenesis, no lasting changes were present in adult neurogenesis after ES and the cognitive impairments were less prominent and only apparent in some cognitive tasks. We further show that, although neurogenesis and cognition correlate positively, only the hippocampus‐dependent functions depend on changes in neurogenesis, whereas cognitive functions that are not exclusively hippocampus‐dependent do not. This study indicates that chronic ES has lasting consequences on hippocampal structure and function in mice and suggests that male mice are more susceptible to ES than females. Unraveling the mechanisms that underlie the persistent ES‐induced effects may have clinical implications for treatments to counteract ES‐induced deficits. © 2014 Wiley Periodicals, Inc.