Djoher Nora Abrous

French Institute of Health and Medical Research | Inserm · Neurocentre Magendie U862

Aging is commonly associated with a decline in memory abilities, yet some individuals remain resilient with preserved memory abilities. Memory processing is critically dependent on adult neurogenesis, a unique form of plasticity in the hippocampus. However, it remains unknown if cognitive aging influences the integration and role of adult-born hipp...

The dentate gyrus (DG) of the hippocampus is a mosaic of dentate granule neurons (DGNs) accumulated throughout life. While many studies focused on the morpho-functional properties of adult-born DGNs, much less is known about DGNs generated during development, and in particular those born during embryogenesis. One of the main reasons for this gap is...

The dentate gyrus (DG) of the hippocampus is a mosaic of dentate granule neurons (DGNs) accumulated throughout life. While many studies focused on the morpho-functional properties of adult-born DGNs, much less is known about DGNs generated during development, and in particular those born during embryogenesis. One of the main reasons for this gap is...

Hippocampal adult neurogenesis is involved in many memory processes from learning, to remembering and forgetting. However, whether or not the stimulation of adult neurogenesis is a sufficient condition to improve memory performance remains unclear. Here, we developed and validated, using ex-vivo electrophysiology, a chemogenetic approach that combi...

Decline in episodic memory is one of the hallmarks of aging and represents one of the most important health problems facing Western societies. A key structure in episodic memory is the hippocampal formation and the dentate gyrus in particular, as the continuous production of new dentate granule neurons in this brain region was found to play a cruci...

Stress is an unavoidable condition in human life. Stressful events experienced during development, including in utero, have been suggested as one major pathophysiological mechanism for developing vulnerability towards neuropsychiatric and neurodevelopmental disorders in adulthood. One cardinal feature of such disorders is impaired cognitive ability...

The dentate gyrus is one of the only brain regions that continues its development after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated the role of dentate granule neurons (DGNs) born during adolescence in spatial memory and compared them with those generated earlier in lif...

Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for survival, positioning, somatodendritic morphogenesis, and functional maturation of ad...

Hippocampal adult neurogenesis is involved in many memory processes from learning, to remembering and forgetting. However, whether or not the stimulation of adult neurogenesis can improve memory performance remains unclear. Here, using a chemogenetic approach that combines selective tagging and specific activation of distinct adult-born neuron popu...

Hippocampal adult neurogenesis has been associated to many cognitive, emotional, and behavioral functions and dysfunctions, and its status as a selected effect or an “appendix of the brain” has been debated. In this review, we propose to understand hippocampal neurogenesis as the process underlying the “Baldwin effect”, a particular situation in ev...

Memory reconsolidation, the process by which memories are again stabilized after being reactivated, has strengthened the idea that memory stabilization is a highly plastic process. To date, the molecular and cellular bases of reconsolidation have been extensively investigated particularly within the hippocampus. However, the role of adult neurogene...

The mechanistic target of rapamycin (mTOR) is a ubiquitously expressed kinase that acts through two complexes, mTORC1 and mTORC2, to regulate protein homeostasis, as well as long lasting forms of synaptic and behavioral plasticity. Alteration of the mTOR pathway is classically involved in neurodegenerative disorders, and it has been linked to dysre...

Decline in episodic memory is one of the hallmarks of aging and represents one of the most important health problems facing western societies. A key structure in episodic memory is the hippocampal formation and the dentate gyrus in particular, as the continuous production of new dentate granule neurons in this brain region was found to play a cruci...

Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo , we show that the atypical Rho GTPase Rnd2 is crucial for the survival, positioning, somatodendritic morphogenesis and functional maturation o...

During aging, some individuals are resilient to the decline of cognitive functions whereas others are vulnerable. These inter‐individual differences in memory abilities have been associated with differences in the rate of hippocampal neurogenesis measured in elderlies. Whether the maintenance of the functionality of neurons generated throughout adu...

The dentate gyrus presents the peculiarity to be formed after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated and compared the role of dentate neurons born during adolescence or generated during adulthood. We demonstrated that the ontogenetic stage of dentate neurons in rel...

The mechanistic target or rapamycin (mTOR) is a ubiquitously expressed kinase that acts through two complexes, mTORC1 and mTORC2, to regulate protein homeostasis as well as long lasting forms of synaptic and behavioral plasticity. Alteration of the mTOR pathway is classically involved in neurodegenerative disorders, and it has been linked to dysreg...

Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors (TFs) are broadly expressed across neuron subtypes and brain regions. Thus, how region- and neuronal subtype-specific plasticity are established...

During aging some individuals are resilient to the decline of cognitive functions whereas others are vulnerable. These inter-individual differences in memory abilities have been associated with differences in the rate of hippocampal neurogenesis measured at old age. Whether the maintenance of the functionality of neurons generated throughout adult...

Mild-traumatic brain injury (mTBI) represents ~80% of all emergency room visits and increases the probability of developing long-term cognitive disorders in children. To date, molecular and cellular mechanisms underlying post-mTBI cognitive dysfunction are unknown. Astrogliosis has been shown to significantly alter astrocytes' properties following...

Adult hippocampal neurogenesis plays a critical role in a wide spectrum of hippocampus-dependent functions. Brain pathologies that involve the hippocampus like epilepsy, stroke, and traumatic brain injury, are commonly associated with cognitive impairments and mood disorders. These insults can affect neural stem cells and the subsequent neurogenic...

The hippocampus is the main locus for adult dentate gyrus (DG) neurogenesis. A number of studies have shown that aberrant DG neurogenesis correlates with many neuropsychiatric disorders, including drug addiction. Although clear causal relationships have been established between DG neurogenesis and memory dysfunction or mood-related disorders, evide...

In nonhuman mammals and in particular in rodents, most granule neurons of the dentate gyrus (DG) are generated during development and yet little is known about their properties compared with adult-born neurons. Although it is generally admitted that these populations are morphologically indistinguishable once mature, a detailed analysis of developm...

Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-ge...

Progenitors of cortical glutamatergic neurons (Glu progenitors) are usually thought to switch fate before birth to produce astrocytes. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate duri...

Ciliary neurotrophic factor (CNTF) potently decreases food intake and body weight in diet-induced obese mice by acting through neuronal circuits and pathways located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts pro-inflammatory actions within the brain. Here we tested whether CNTF modifies energy balance by inducing inflammato...

Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-l...

Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. Here we tested whether the intertwining of these two processes has a role in the metabolic changes caused by three weeks of saturated high-fat diet (HFD) consumption.As compared to chow, HFD-fed mice rapidly increased body weight and fa...

Maternal stress is associated with an altered mother-infant relationship that endangers offspring development, leading to emotional/behavioral problems. However, little research has investigated the stress-induced alterations of the maternal brain that could underlie such a disruption of mother-infant bonding. Olfactory cues play an extensive role...

LAMP5 is member of the LAMP family of membrane proteins. In contrast to the canonical members of this protein family, LAMP1 and LAMP2, which show widespread expression in many tissues, LAMP 5 is brain specific in mice. In C. elegans, the LAMP5 ortholog UNC-46 has been suggested to act a trafficking chaperone, essential for the correct targeting of...

Laboratory rodents provided chronic unlimited access to running wheels display increased neurogenesis in the hippocampal dentate gyrus. In addition, recent studies indicate that such an access to wheels stimulates dendritic arborization in newly formed neurons. However, (i) the presence of the running wheel in the housing environment might also bea...

During the last decade, the questions on the functionality of adult neurogenesis have changed their emphasis from if to how the adult-born neurons participate in a variety of memory processes. The emerging answers are complex because we are overwhelmed by a variety of behavioral tasks that apparently require new neurons to be performed optimally. W...

Adult neurogenesis occurs in the dentate gyrus of the hippocampus, which is a key structure in learning and memory. Adult-generated granule cells have been shown to play a role in spatial memory processes such as acquisition or retrieval, in particular during an immature stage when they exhibit a period of increased plasticity. Here, we demonstrate...

New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult-born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here we explored whether such modulatory effects exist in mice. New GCs were t...

The serotonin2C receptor (5-HT2CR) is known to control dopamine (DA) neuron function by modulating DA neuronal firing and DA exocytosis at terminals. Recent studies assessing the influence of 5-HT2CRs on cocaine-induced neurochemical and behavioral responses have shown that 5-HT2CRs can also modulate mesoaccumbens DA pathway activity at post-synapt...

In keeping with its ability to control the mesoaccumbens dopamine (DA) pathway, the serotonin2C receptor (5-HT2CR) plays a key role in mediating the behavioral and neurochemical effects of drugs of abuse. Studies assessing the influence of 5-HT2CR agonists on cocaine-induced responses have suggested that 5-HT2CRs can modulate mesoaccumbens DA pathw...

New neurons are continuously produced in the adult dentate gyrus of the hippocampus, a key structure in learning and memory. It has been shown that adult neurogenesis is crucial for normal memory processing. However, it is not known whether neurons born during the developmental period and during adulthood support the same functions. Here, we demons...

The dentate gyrus (DG) and the olfactory bulb (OB) are two regions of the adult brain in which new neurons are integrated daily in the existing networks. It is clearly established that these newborn neurons are implicated in specific functions sustained by these regions and that different factors can influence neurogenesis in both structures. Among...

In utero electroporation (IUE) has become a powerful technique to study the development of different regions of the embryonic nervous system 1-5. To date this tool has been widely used to study the regulation of cellular proliferation, differentiation and neuronal migration especially in the developing cerebral cortex 6-8. Here we detail our protoc...

A key question in the field of neurogenesis, stress and depression has been whether a reduction in neurogenesis per se can produce a ‘depressed’ animal.1, 2, 3, 4 Recently, Snyder et al.⁵ convincingly demonstrated that new hippocampal neurons are necessary for an efficient recovery of hypothalamic–pituitary–adrenal (HPA) axis activity after stress....

Adult hippocampal neurogenesis, which is involved in the physiopathology of hippocampal functions, is genetically determined and influenced by early life events. However, studies on the interaction of these determining forces are lacking. This prompted us to investigate whether adult hippocampal neurogenesis can be modulated by maternal care and wh...

Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an ac...

Adult neurogenesis occurs in the dentate gyrus of the hippocampus, which is a key structure in learning and memory. It is believed that adult-born neurons exert their unique role in information processing due to their high plasticity during immature stage that renders them malleable in response to environmental demands. Here, we demonstrate that, i...

New neurons are continuously produced in the adult dentate gyrus of the hippocampus. It has been shown that one of the functions of adult neurogenesis is to support spatial pattern separation, a process that transforms similar memories into nonoverlapping representations. This prompted us to investigate whether adult-born neurons are required for d...

Hyperforin is one of the main bioactive compounds that underlie the antidepressant actions of the medicinal plant Hypericum perforatum (St. John's wort). However, the effects of a chronic hyperforin treatment on brain cells remains to be fully addressed. The following study was undertaken to further advance our understanding of the biological effec...

Until recently, it was believed that the introduction of new neurons in neuronal networks was incompatible with memory function. Since the rediscovery of adult hippocampal neurogenesis, behavioral data demonstrate that adult neurogenesis is required for memory processing. We examine neurocomputational studies to identify which basic mechanisms invo...

Adult neurogenesis is a process by which the brain produces new neurons once development has ceased. Adult hippocampal neurogenesis has been linked to the relational processing of spatial information, a role attributed to the contribution of newborn neurons to long-term potentiation (LTP). However, whether newborn neurons also influence long-term d...

Understanding the cellular mechanisms underlying learning and memory is a major challenge in neurobiology. Structural and functional changes occurring in the hippocampus such as synaptic remodeling and long-term potentiation are key signatures of long-term memory processes. The discovery of a de novo hippocampal production of neurons in the adult b...

In the mammalian brain, the dentate gyrus and the olfactory bulb are regions where new neurons are continuously added. While the functional consequences of continuous hippocampal neurogenesis have been extensively studied, the role of olfactory adult-born neurons remains elusive. In particular, the involvement of these newborn neurons in odor proce...

Recent years have produced rapid and enormous growth in our understanding of the mechanisms regulating adult neurogenesis. Emerging fields of research now aim at clarifying the relationships between neurogenesis and diseases. This paper deals with neurogenesis and stress-related disorders. After a brief overview of the stress response, we first pro...

Scribble (Scrib) is a key regulator of apicobasal polarity, presynaptic architecture, and short-term synaptic plasticity in Drosophila. In mammals, its homolog Scrib1 has been implicated in cancer, neural tube closure, and planar cell polarity (PCP), but its specific role in the developing and adult nervous system is unclear. Here, we used the circ...

Neurogenesis in the hippocampus is characterized by the birth of thousand of cells that generate neurons throughout life. The fate of these adult newborn neurons depends on life experiences. In particular, spatial learning promotes the survival and death of new neurons. Whether learning influences the development of the dendritic tree of the surviv...

Chronic voluntary wheel-running activity has been reported to hypersensitise central CB1 receptors in mice. On the other hand, pharmacological findings suggest that the CB1 receptor could be involved in wheel-running behaviour and in running-induced neurogenesis in the hippocampus. We analysed wheel-running behaviour for 6 weeks and measured its co...

The dogma according to which "once the development of the central nervous system ended, generation of neurons was impossible" has been challenged by the discovery that new neurons are created in specific regions of the adult mammalian brain. This discovery has been one of the most controversial of modern neuroscience. One of these regions is the de...

In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing ne...

Irradiation did not alter the morphology of DCX+ cells reaching the OB. Dendrites were counted for DCX+ cells in the GCL, EPL and GL of sham and irradiated mice, 7 months after irradiation. P>0.05 with Student's t-test (n = 25 from 5 random cells analyzed per OB layer and from 5 mice per group). (2.75 MB EPS)

Complete statistical analysis on spontaneous discrimination. (0.08 MB RTF)

Focal SVZ irradiation inhibited the recruitment of new neurons in the OB but not in the hippocampus. New cells were labeled with BrdU 3 days after the final focal irradiation and survival was evaluated 11 days later. The mean number of BrdU+ cells in the GCL of the OB and in the dentate gyrus of the hippocampus was determined for sham and irradiate...

Complete statistical analysis on neurogenesis data. (0.04 MB RTF)

Complete statistical analysis for operant conditioning. (0.11 MB RTF)

Statistical analysis on 2-odor memory test. (0.03 MB RTF)

Adult hippocampal neurogenesis is a unique example of structural plasticity, the functional role of which has been a matter of intense debate. New transgenic models have recently shown that neurogenesis participates in hippocampus-mediated learning. Here, we show that transgenic animals, in which adult hippocampal neurogenesis has been specifically...

Stressors occurring during pregnancy can alter the developmental trajectory of offspring and lead to, among other deleterious effects, cognitive deficits and hyperactivity of the hypothalamo-pituitary-adrenal axis. A recent feature of the prenatal stress (PS) model is its reported influence on structural plasticity in hippocampal formation, which s...

Adult hippocampal neurogenesis is influenced by a variety of stimuli, including exercise, but the mechanisms by which running affects neurogenesis are not yet fully understood. Because beta-endorphin, which is released in response to exercise, increases cell proliferation in vitro, we hypothesized that it could exert a similar effect in vivo and me...

In vivo individual genomic integration of EYFPBax-TetO-ECFPBax or Nestin-rtTA-βGeo constructs does not influence behavioral abilities and adult neurogenesis. Wild-type (Wt), Bax and rtTA mice treated or untreated with Dox were compared to Bigenic rtTA/Bax mice treated with vehicle (Big-Veh). (A) Number of dividing cells in the DG identified by HH3...