Elizabeth Gould

Princeton University | PU · Department of Psychology

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but no previous studies have assigned a behavioral function to this circuit. Here we show that abGC input to the CA2 is necessary for the retrieval of remote social memories. Ablation of abGCs impaired retrieval of developmental social memories, while this ability return...

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but no previous studies have assigned a behavioral function to this circuit. Here we show that abGC input to the CA2 is necessary for the retrieval of remote social memories. Ablation of abGCs impaired retrieval of developmental social memories, while this ability return...

Social memories formed in early life, like those for family and unrelated peers, are known to contribute to healthy social interactions throughout life, although how the developing brain supports social memory remains relatively unexplored. The CA2 subregion of the hippocampus is involved in social memory function, but most literature on this subje...

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but no previous studies have assigned a behavioral function to this circuit. Here we show that abGC input to the CA2 is necessary for the retrieval of remote social memories. Ablation of abGCs impaired retrieval of developmental social memories, while this ability return...

Mutation or deletion of the SHANK3 gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments. Shank3B knockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major out...

Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when...

It is now well-established that the hippocampal CA2 region plays an important role in social recognition memory in adult mice. The CA2 is also important for the earliest social memories, including those that mice have for their mothers and littermates, which manifest themselves as a social preference for familiarity over novelty. The role of the CA...

It is now well-established that early life adversity (ELA) predisposes individuals to develop several neuropsychiatric conditions, including anxiety disorders, and major depressive disorder. However, ELA is a very broad term, encompassing multiple types of negative childhood experiences, including physical, sexual and emotional abuse, physical and...

Social memory dysfunction is a feature of several neuropsychiatric and neurodevelopmental disorders. Mutation or deletion of the SHANK3 gene, which codes for a synaptic scaffolding protein, has been linked to autism spectrum disorder (ASD) and Phelan-McDermid syndrome, conditions associated with impairments in social memory. Shank3B knockout (KO) m...

Early-life adversity (ELA) predisposes individuals to develop neuropsychiatric conditions, which are more prevalent in women than men. Efforts to model this sex difference in rodents have produced mixed results, with some studies paradoxically showing stronger phenotypes in males than females. Since changes in reproductive hormone levels can increa...

Early-life adversity (ELA) predisposes individuals to develop neuropsychiatric conditions, which are more prevalent in women than men. Efforts to model this sex difference in rodents have produced mixed results, with some studies paradoxically showing stronger phenotypes in males than females. Since changes in reproductive hormone levels can increa...

Early life adversity (ELA) increases the risk of developing neuropsychiatric illnesses such as anxiety disorders. However, the mechanisms connecting these negative early life experiences to illness later in life remain unclear. In rodents, plasticity mechanisms, specifically adult neurogenesis in the ventral hippocampus, have been shown to be alter...

Diffuse and structured extracellular matrix (ECM) comprise ∼20% of the brain’s volume and play important roles in development and adult plasticity. Perineuronal nets (PNNs), specialized ECM structures that surround certain types of neurons in the brain, emerge during the postnatal period, making their development and maintenance potentially sensiti...

Background Excessive repetitive behavior is a debilitating symptom of several neuropsychiatric disorders. Parvalbumin-positive inhibitory interneurons in the dorsal striatum have been linked to repetitive behavior, and a sizeable portion of these cells are surrounded by perineuronal nets (PNNs), specialized extracellular matrix structures. Although...

Social memory dysfunction is an especially devastating symptom of many neuropsychiatric disorders, which makes understanding the cellular and molecular processes that contribute to such abnormalities important. Evidence suggests that the hippocampus, particularly the CA2 region, plays an important role in social memory. We sought to identify potent...

The cover image is based on the Research Article Adult‐born granule cell mossy fibers preferentially target parvalbumin‐positive interneurons surrounded by perineuronal nets by Brandy A. Briones et al., https://doi.org/10.1002/hipo.23296.

Some of the most enduring social connections begin when infants first recognize their caregivers, memories that form the basis of many family relationships. It remains unknown whether these early social memories persist into adulthood in mice and, if so, which brain regions support them. Here we show that mice form memories of their mother within d...

Adult‐born granule cells (abGCs) integrate into the hippocampus and form connections with dentate gyrus parvalbumin‐positive (PV+) interneurons, a circuit important for modulating plasticity. Many of these interneurons are surrounded by perineuronal nets (PNNs), extracellular matrix structures known to participate in plasticity. We compared abGC pr...

Throughout adulthood, the dentate gyrus continues to produce new granule cells, which integrate into the hippocampal circuitry. New neurons have been linked to several known functions of the hippocampus, including learning and memory, anxiety and stress regulation, and social behavior. We explored whether transgenic reduction of adult-born neurons...

Childhood maltreatment increases the likelihood of developing anxiety disorders in humans. Early life adversity (ELA) paradigms in rodents produce lasting increases in avoidant and inhibitory responses to both immediate and nonspecific threats, collectively referred to as defensive behaviors. This approach provides an opportunity to thoroughly inve...

Although commonly associated with development, structural growth is a feature of the brain that endures well into adulthood. Numerous studies have shown that dendritic complexity and synapse number change as a result of experience in a number of brain regions to varying degrees, and some studies have causally linked these forms of structural plasti...

In the adult mammalian hippocampus, new neurons arise from stem and progenitor cell division, in a process known as adult neurogenesis. Adult-generated neurons are sensitive to experience and may participate in hippocampal functions, including learning and memory, anxiety and stress regulation, and social behavior. Increasing evidence emphasizes th...

This cover image is based on the Research Article The effects of living in an outdoor enclosure on hippocampal plasticity and anxiety‐like behavior in response to nematode infection by Elise C. Cope et al., DOI: 10.1002/hipo.23033.

Background: In humans, accumulated adverse experiences during childhood increase the risk of anxiety disorders and attention-deficit/hyperactivity disorder. In rodents, the ventral hippocampus (vHIP) is associated with anxiety regulation, and lesions in this region alter both anxiety-like behavior and activity levels. Neuronal oscillations in the...

The production of new neurons, or neurogenesis, has been shown in multiple mammalian species in adulthood in the dentate gyrus of the hippocampus. Stress has been shown to alter brain plasticity and furthermore inhibit neurogenesis in the hippocampus in which changes appear to be mediated not only by glucocorticoid hormones but also by the context...

The hippocampus of rodents undergoes structural remodeling throughout adulthood, including the addition of new neurons. Adult neurogenesis is sensitive to environmental enrichment and stress. Microglia, the brain's resident immune cells, are involved in adult neurogenesis by engulfing dying new neurons. While previous studies using laboratory envir...

Obesity affects more than 600 million people worldwide, a staggering number that appears to be on the rise. One of the lesser known consequences of obesity is its deleterious effects on cognition, an effect that has been well-documented across many cognitive domains and age groups. To investigate the cellular mechanisms that underlie obesity-associ...

Increases in the number and/or the size of dendritic spines, sites of excitatory synapses, have been linked to different types of learning as well as synaptic plasticity in several brain regions, including the hippocampus, sensory cortex, motor cortex, and cerebellum. By contrast, a previous study reported that training on a maze task that requires...

The medial prefrontal cortex (mPFC) is important for cognitive flexibility, the ability to switch between two task-relevant dimensions. Changes in neuronal oscillations and alterations in the coupling across frequency ranges have been correlated with attention and cognitive flexibility. Here we show that astrocytes in the mPFC of adult male Sprague...

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...

While we have known for some time that new neurons are produced in the dentate gyrus of the hippocampus throughout adulthood, the role of adult neurogenesis in relation to known hippocampal functions, such as spatial navigation learning and memory, is still an area of active investigation. New neurons are highly sensitive to experience, and evidenc...

Animals, including humans, require a highly coordinated and flexible system of social behavior and threat evaluation. However, trauma can disrupt this system, with the amygdala implicated as a mediator of these impairments in behavior. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its imm...

Autism spectrum disorder (ASD) is often associated with cognitive deficits and excessive anxiety. Neuroimaging studies have shown atypical structure and neural connectivity in the hippocampus, medial prefrontal cortex (mPFC), and striatum, regions associated with cognitive function and anxiety regulation. Adult hippocampal neurogenesis is involved...

Unlabelled: Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hie...

A variety of experiences have been shown to affect the production of neurons in the adult hippocampus. These effects may be mediated by experience-driven hormonal changes, which, in turn, interact with factors such as sex, age and life history to alter brain plasticity. Although the effects of physical experience and stress have been extensively ch...

Significance In humans, obesity impairs cognition and produces atrophy of brain regions associated with learning and memory, but few studies have investigated the underlying cellular mechanisms. We used a diet-induced model of obesity in rats to study excessive weight gain and found that early stage obesity, before the onset of diabetes or metaboli...

The medial prefrontal cortex is important for cognitive flexibility, a capability that is affected by environmental conditions and specific experiences. Aversive experience, such as chronic restraint stress, is known to impair performance on a task of cognitive flexibility, specifically attentional set-shifting, in rats. Concomitant with this perfo...

Physical exercise enhances a wide range of cognitive functions in humans. Running-induced cognitive enhancement has also been demonstrated in rodents but with a strong emphasis on tasks that require the hippocampus. Additionally, studies designed to identify mechanisms that underlie cognitive enhancement with physical exercise have focused on runni...

A rapidly growing body of literature indicates that adult neurogenesis in the hippocampus is sensitive to a variety of environmental factors. The effects of emotionally salient experiences, such as stress and physical exercise, have been characterized extensively with regard to both adult neurogenesis and behaviors associated with the hippocampus....

Anxiety disorders are highly prevalent but little is known about their underlying mechanisms. Gap junctions exist in brain regions important for anxiety regulation, such as the ventral hippocampus (vHIP) and mPFC, but their functions in these areas have not been investigated. Using pharmacological blockade of neuronal gap junctions combined with el...

Infections during pregnancy have been associated with increased risks of neuropsychiatric disorders in offspring, although the underlying mechanisms have not been determined. Gallagher et al. (2013) show that maternal exposure to the infection-induced inflammatory cytokine IL-6 produces lasting effects on forebrain stem cell pools of offspring duri...

Stress is known to inhibit neuronal growth in the hippocampus. In addition to reducing the size and complexity of the dendritic tree, stress and elevated glucocorticoid levels are known to inhibit adult neurogenesis. Despite the negative effects of stress hormones on progenitor cell proliferation in the hippocampus, some experiences which produce r...

Physical exercise is known to reduce anxiety. The ventral hippocampus has been linked to anxiety regulation but the effects of running on this subregion of the hippocampus have been incompletely explored. Here, we investigated the effects of cold water stress on the hippocampus of sedentary and runner mice and found that while stress increases expr...

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 neu...

Adult neurogenesis is often studied by labeling new cells with the thymidine analog bromodeoxyuridine (BrdU) and using immunohistochemical methods for their visualization. Using this approach, considerable variability has been reported in the number of new cells produced in the dentate gyrus of adult rodents. We examined whether immunohistochemical...

Using a new retrovirus-optogenetics technique, researchers have found that new neurons in the adult hippocampus are important for memory, but only at an immature stage, when they show enhanced synaptic plasticity.

Oxytocin has been linked to social behavior, including social recognition, pair bonding and parenting, but its potential role in promoting neuronal growth has not been investigated. We show here that oxytocin, but not vasopressin, stimulates both cell proliferation and adult neurogenesis in the hippocampus of rats. Oxytocin is also capable of stimu...

Adult neurogenesis has been the focus of intense investigation, but the function of new neurons remains elusive. Snyder et al. (2011) report that new neurons in the hippocampus play an important role in appropriate shut-off of the stress response.

Paternal care is rare among mammals, occurring in ≈6% of species. California mice (Peromyscus californicus) are unusual; fathers participate extensively in raising their young and display the same components of parental care as mothers, with the exception of nursing. Parenting is a complex experience, having stressful and enriching aspects. The hip...

Numerous studies have attempted to determine the function of adult neurogenesis in the hippocampus using methods to deplete new neurons and examine changes in behaviors associated with this brain region. This approach has produced a set of findings that, although not entirely consistent, suggest new neurons are associated with improved learning and...

The dentate gyrus of the hippocampus continues to produce new neurons throughout adulthood. Adult neurogenesis has been linked to hippocampal function, including learning and memory, anxiety regulation and feedback of the stress response. It is thus not surprising that stress, which affects hippocampal function, also alters the production and survi...

As any new parent knows, having a baby provides opportunities for enrichment, learning and stress - experiences known to change the adult brain. Yet surprisingly little is known about the effects of maternal experience, and even less about the effects of paternal experience, on neural circuitry not directly involved in parenting. Here we discuss ho...

The postpartum period is associated with numerous hormonal changes, some of which have been linked to detrimental effects on the medial prefrontal cortex (mPFC), a brain region involved in cognition. Here, we investigated whether mPFC structure and function are negatively influenced during the postpartum period, an outcome that might be predicted b...

Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and func...

Most neurons in the mammalian brain are produced during the embryonic period. In contrast, the granule cell population of the dentate gyrus of the hippocampal formation is produced during an extended period that begins during gestation and continues well into adulthood. The production of new granule neurons is suppressed by stress. These observatio...

Cell proliferation occurs in the adult brain, as does neurogenesis, and cells that give rise to neurons and glia in vivo and in vitro have been identified in the adult central nervous system (CNS). Studies have identified cells with stem cell-like properties in the adult mammalian brain. The bulk of evidence suggests that these cells exhibit charac...

Physical exercise enhances adult neurogenesis in the hippocampus. Running induces the uptake of blood insulin-like growth factor-I (IGF-I) into the brain. A causal link between these two phenomena has been reported; running-induced increases in adult neurogenesis can be blocked by peripheral infusion of anti-IGF-I. Running also alters other aspects...

Adult neurogenesis is often studied by labeling new cells with the thymidine analog bromodeoxyuridine (BrdU) and using immunohistochemical methods for their visualization. Using this approach, considerable variability has been reported in the number of new cells produced in the dentate gyrus of adult rodents. We examined whether immunohistochemical...

The hippocampus is a region of the mammalian brain that shows an impressive capacity for structural reorganization. Preexisting neural circuits undergo modifications in dendritic complexity and synapse number, and entirely novel neural connections are formed through the process of neurogenesis. These types of structural change were once thought to...

Nature Neuroscience offers a unique mix of opinion and reviews alongside top-quality research papers. Published monthly, in print and online, the journal reflects the entire spectrum of neuroscience, from molecular to cognitive.

With aging there is a decline in the number of newly generated neurons in the dentate gyrus of the hippocampus. In rodents and tree shrews, this age-related decrease in neurogenesis is evident long before the animals become aged. No previous studies have investigated whether primates exhibit a similar decline in hippocampal neurogenesis with aging....

Physical activity enhances hippocampal function but its effects on neuronal structure remain relatively unexplored outside of the dentate gyrus. Using Golgi impregnation and the lipophilic tracer DiI, we show that long-term voluntary running increases the density of dendritic spines in the entorhinal cortex and hippocampus of adult rats. Exercise w...

Oestrogens have numerous effects on the brain, beginning during gestation and continuing on into adulthood. Many of these actions involve areas of the brain that are not primarily involved in reproduction, such as the basal forebrain, hippocampus, caudate putamen, midbrain raphe and brainstem locus coeruleus. This paper describes three actions of o...

It is now widely accepted that neurogenesis occurs in two regions of the adult mammalian brain--the hippocampus and the olfactory bulb. There is evidence for adult neurogenesis in several additional areas, including the neocortex, striatum, amygdala and substantia nigra, but this has been difficult to replicate consistently other than in the damage...

Motherhood is accompanied by alterations in numerous nonreproductive behaviors, including learning and memory, as well as anxiety and stress regulation. These functions have been linked to adult neurogenesis in the hippocampus, but the effect of maternal experience on this brain region has not been completely explored. To determine whether the prod...

Some, but not all, types of learning and memory can influence neurogenesis in the adult hippocampus. Trace eyeblink conditioning has been shown to enhance the survival of new neurons, whereas delay eyeblink conditioning has no such effect. The key difference between the two training procedures is that the conditioning stimuli are separated in time...

Prolonged sleep deprivation is stressful and has been associated with adverse consequences for health and cognitive performance. Here, we show that sleep deprivation inhibits adult neurogenesis at a time when circulating levels of corticosterone are elevated. Moreover, clamping levels of this hormone prevents the sleep deprivation-induced reduction...

Like human fathers, male marmosets help raise their young, yet the ways in which fatherhood influences the brain remain largely unknown. We show that first-time and experienced marmoset fathers have enhanced density of dendritic spines on pyramidal neurons in prefrontal cortex as compared to non-fathers. In parallel, the abundance of vasopressin V1...

Social isolation can exacerbate the negative consequences of stress and increase the risk of developing psychopathology. However, the influence of living alone on experiences generally considered to be beneficial to the brain, such as physical exercise, remains unknown. We report here that individual housing precludes the positive influence of shor...

During the past several years, evidence has accumulated suggesting a relationship between newly born cells in the hippocampus and various types of learning and memory. However, most of the evidence is correlational and some of it does not agree. This review discusses both sides of this issue, considering the effects of learning on the production of...

Stress hormones have potent growth-inhibiting effects on a variety of peripheral tissues. Consistent with this general function, stress has been shown to inhibit cell proliferation and, ultimately, neurogenesis in the hippocampus. This effect appears to be common across mammalian species, life stages, and most types of stressors. Although some evid...