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Publications (97)
Exercise can be leveraged as an important tool to improve neural and psychological health, either on its own or to bolster the efficacy of evidence‐based treatment modalities. Research in both humans and animal models shows that positive experiences, such as exercise, promote neuroprotection while, in contrast, aversive experiences, particularly th...
The developmental trajectory of weight‐bearing locomotion and sensorimotor reflexes following a spinal cord injury, as well as the mechanisms for plasticity, remain unclear. In rats, the second postnatal week is a critical period for the development and recovery of spinal sensorimotor function. The purpose of the present study was to characterize d...
In early development, the spinal cord in healthy or disease states displays remarkable activity‐dependent changes in plasticity, which may be in part due to the increased activity of brain derived neurotrophic factor (BDNF). Indeed, BDNF delivery has been efficacious in partially ameliorating many of the neurobiological and behavioral consequences...
Early life stress (ELS) in the form of trauma or caregiver abuse and neglect is often associated with psychopathology. However, not everyone exposed to ELS develops a pathology; others display resilience, or the ability to adapt and persevere despite ongoing adversity. Several molecular moderator variables between ELS and behavioral phenotypes have...
A total of 1 in 20 infants born annually are exposed to alcohol prenatally, which disrupts neurodevelopment and results in several disorders categorized under the umbrella term Fetal Alcohol Spectrum Disorders (FASD). Children and adolescents affected by FASD exhibit delayed maturation of cerebral white matter, which contributes to deficits in exec...
Early life stress (ELS) in the form of trauma or caregiver abuse and neglect is often associated with psychopathology. However, not everyone exposed to ELS develops a pathology; others display resilience, or the ability to adapt and persevere despite ongoing adversity. Several molecular moderator variables between ELS and behavioral phenotypes have...
Early life stress (ELS) encompasses exposure to aversive experiences during early development, such as neglect or maltreatment. Animal and human studies indicate that ELS has maladaptive effects on brain development, leaving individuals more vulnerable to developing behavioral and neuropsychiatric disorders later in life. This result occurs in part...
Exposure to adversity in early development has powerful and potentially lasting consequences on behavior. Previous work in our laboratory using female Long‐Evans rats has demonstrated that exposure to early‐life maltreatment manifests into alterations in dam behavior, including a perpetuation of the maltreatment phenotype. These observed behavioral...
Early-life adversity (ELA), often clinically referred to as “adverse childhood experiences (ACE),” is the exposure to stress-inducing events in childhood that can result in poor health outcomes. ELA negatively affects neurodevelopment in children and adolescents resulting in several behavioral deficits and increasing the risk of developing a myriad...
Epigenetic mechanisms play an important regulatory role in neural processes associated with brain development and phenotypic outcome, and do so from early embryonic development through senescence. Though a complete picture has yet to emerge, it is clear that epigenetic changes promote a range of processes important for brain evolution, development,...
Conflicting ideas surrounding the inheritance of acquired characteristics is not new; for nearly two centuries, debate surrounding the validity and mechanism behind inheritance of acquired characteristics was pioneered by Lamarck, Darwin, and Weismann. Epigenomics, a field examining changes in gene expression as a result of environmental context, h...
Child maltreatment not only leads to epigenetic changes, but also increases the risk of related behavioral deficits and mental disorders. These issues presumably are most closely associated with epigenetic changes in the brain, but epigenetic changes in peripheral tissues like blood are often examined instead, due to their accessibility. As such, t...
Epigenetic modifications play a role in complex processes such as genomic imprinting and control of transcriptional regimes. These modifications are critical to optimal brain development and behavioral outcomes. Indeed, aberrant epigenetic marks play a role in the etiology of many neurodevelopmental disorders, some of which we still do not fully un...
One of the most well‐known environmental effectors of epigenetic change is stress, particularly during early development. Deviations from optimal developmental trajectories brought about by stress have long‐term behavioral consequences, and epigenetic adaptations are a promising biological mechanism through which this occurs. Given that individuals...
Behavioral epigenetics posits that both nature and nurture must be considered when determining the etiology of behavior or disease. The epigenome displays a remarkable ability to respond to environmental input in early sensitive periods but also throughout the lifespan. These responses are dependent on environmental context and lead to behavioral o...
The sixth edition of the foundational reference on cognitive neuroscience, with entirely new material that covers the latest research, experimental approaches, and measurement methodologies. Each edition of this classic reference has proved to be a benchmark in the developing field of cognitive neuroscience. The sixth edition of The Cognitive Neuro...
The field of epigenetics examines how environmental factors influence gene expression. This occurs via modifications to the epigenome, including DNA methylation and histone acetylation. Environmental exposures throughout the lifespan, but particularly during important developmental stages, can result in epigenetic changes, some of which are associa...
Maltreatment during development is associated with epigenetic changes to the genome. Enhancing caregiving may mitigate these effects. Attachment and Biobehavioral Catch-Up (ABC) is an intervention that has been shown to improve parent–child relationships and a variety of biological and behavioral outcomes among children that are involved in Child P...
Although the importance of epigenetic mechanisms in behavioral development has been gaining attention in recent years, research has largely focused on the brain. To our knowledge, no studies to date have investigated epigenetic changes in the developing spinal cord to determine the dynamic manner in which the spinal epigenome may respond to environ...
The quality of parental care received during development profoundly influences an individual’s phenotype, including that of maternal behavior. We previously found that female rats with a history of maltreatment during infancy mistreat their own offspring. One proposed mechanism through which early-life experiences influence behavior is via epigenet...
Reorganization of the brain's epigenetic landscape occurs alongside early adversity in both human and non-human animals. Whether this reorganization is simply incidental to or is a causal mechanism of the behavioral abnormalities that result from early adversity is important to understand. Using the scarcity-adversity model of low nesting resources...
The effects of exposure to developmental stress often diverge for males and females. Using the scarcity‐adversity model of low nesting resources outside the home cage, our lab has discovered sex differences in both behavioral and epigenetic consequences of repeated exposure to caregiver maltreatment. For the measures we have performed to date, we h...
The use of non-human animals in research is a longstanding practice to help us understand and improve human biology and health. Animal models allow researchers, for example, to carefully manipulate environmental factors in order to understand how they contribute to development, behavior, and health. In the field of behavioral epigenetics such appro...
Advances in epigenetic methodologies have deepened theoretical explanations of mechanisms linking early life stress (ELS) and disease outcomes and suggest promising targets for intervention. To date, however, human studies have not capitalized on the richness of diverse animal models to derive and systematically evaluate specific and testable hypot...
Exposure to adversity early in development alters brain and behavioral trajectories. Data continue to accumulate that epigenetic mechanisms are a mediating factor between early-life adversity and adult behavioral phenotypes. Previous work from our laboratory has shown that female Long-Evans rats exposed to maltreatment during infancy display both a...
Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contri...
The long-term effects of developmental alcohol and stress exposure are well documented in both humans and non-human animal models. Damage to the brain and attendant life-long impairments in cognition and increased risk for psychiatric disorders are debilitating consequences of developmental exposure to alcohol and/or psychosocial stress. Here we di...
It is understood that adversity during development has the power to alter behavioral trajectories, and the role of the epigenome in that relationship is currently under intense investigation. Several studies in both nonhuman animals and humans have established a link between early adversity and epigenetic regulation of genes heavily implicated in t...
Nature and nurture work together to drive development, behavior, and health. Behavioral epigenetics research has uncovered underlying mechanisms for how this happens. Children’s early years in development may offer the greatest opportunity for environmental and experiential factors to influence the epigenome (chemical compounds telling our genes wh...
Early life adversity is known to disrupt behavioral trajectories and many rodent models have been developed to characterize these stress-induced outcomes. One example is the scarcity-adversity model of low nesting resources. This model employs resource scarcity (i.e., low nesting materials) to elicit adverse caregiving conditions (including maltrea...
The immediate and long term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions...
Negative experiences with a caregiver during infancy can result in long-term changes in brain function and behavior, but underlying mechanisms are not well understood. It is our central hypothesis that brain and behavior changes are conferred by early childhood adversity through epigenetic changes involving DNA methylation. Using a rodent model of...
DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavior. Here,...
”This project investigated whether our model of FASD (PD4-9) induced changes to Bdnf gene expression in the adult rat hippocampus (PD72) and Bdnf DNA methylation in adulthood and infancy (PD10). In addition, we investigated whether two behavioral interventions (wheel running and environmental complexity) affected these measures of Bdnf regulation i...
The efforts of many neuroscientists are directed toward understanding the appreciable plasticity of the brain and behavior. In recent years, epigenetics has become a core of this focus as a prime mechanistic candidate for behavioral modifications. Animal models have been instrumental in advancing our understanding of environmentally driven changes...
Alcohol exposure in utero can result in Fetal Alcohol Spectrums Disorders (FASD). Measures of hippocampal neuroplasticity, including long-term potentiation, synaptic and dendritic organization, and adult neurogenesis, are consistently disrupted in rodent models of FASD. The current study investigated whether third trimester-equivalent binge-like al...
Environmental factors have long-lasting effects on brain development and behavior. One way experiences are propagated is via epigenetic modifications to the genome. Environmentally driven epigenetic modifications show incredible brain region-and sex-specificity, and many brain regions affected are ones involved in maternal behavior. In rodent model...
Early-life attachment and bonding to a caregiver are necessary for survival in altricial infants and ensure infants rapidly learn to identify and remember the caregiver. This early-life attachment experience also programs brain and behavioral development, in part, mediated through epigenetic processes including DNA methylation. Here we first review...
Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here we show an age-related reduction in the transcription...
Within the past decade we have experienced a paradigm shift in our understanding of gene–environment interactions and pathways through which experiences can become part of our biology. Advances in molecular biology have provided new insights into epigenetic factors (e.g., DNA methylation, histone acetylation) that are remarkably sensitive to enviro...
The present study investigated whether repeated early postnatal exposure to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) alters behavioral responses to the stimulus later in life, at postnatal day (PN30). Long-Evans rat pups with their mothers were exposed for 20 min daily to TMT, water, or a noxious odor, butyric acid (BTA), durin...
Infant–caregiver experiences are major contributing factors to neural and behavioral development. Research indicates that epigenetic mechanisms provide a way in which infant–caregiver experiences affect gene activity and other downstream processes in the brain that influence behavioral development. Our laboratory previously demonstrated in a rodent...
Epigenetic mechanisms such as DNA methylation are part of an emerging story on how early-life experiences can alter behavioral trajectories and lead to the development of disease and psychological disorders. Previous work from our laboratory has demonstrated alterations in methylation of DNA associated with the brain-derived neurotrophic factor (bd...
This article highlights the defining principles, progress, and future directions in epigenetics research in relation to this Special Issue. Exciting studies in the fields of neuroscience, psychology, and psychiatry have provided new insights into the epigenetic factors (e.g., DNA methylation) that are responsive to environmental input and serve as...
While it is well-known that stress during development and adulthood can confer long-term neurobiological and behavioral consequences, investigators have only recently begun to assess epigenetic modifications associated with these consequences. In this review, we highlight clinical research and work with animal models that provide evidence of the im...
Early childhood is a sensitive period in which infant-caregiver experiences have profound effects on brain development and behavior. Clinical studies have demonstrated that infants who experience stress and adversity in the context of caregiving are at an increased risk for the development of psychiatric disorders. Animal models have helped to eluc...
Third trimester-equivalent alcohol exposure causes significant deficits in hippocampal and cortical neuroplasticity, resulting in alterations to dendritic arborization, hippocampal adult neurogenesis, and performance on learning tasks. The current study investigated the impact of neonatal alcohol exposure (postnatal days 4-9, 5.25g/kg/day) on expre...
Epigenetic mechanisms including altered DNA methylation are critical for altered gene transcription subserving synaptic plasticity and the retention of learned behavior. Here we tested the idea that one role for activity-dependent altered DNA methylation is stabilization of cognition-associated hippocampal place cell firing in response to novel pla...
Social factors, particularly those that are encountered early in life such as parental care, can have profound effects on neurobiological trajectories and long-term consequences for mental health. It has been largely accepted that normal brain development depends upon a complex interplay between genetic and environmental factors. The field of behav...
There is increasing evidence that epigenetic mechanisms play an important regulatory role in neural processes associated with brain development and phenotypic outcome, and do so from early embryonic development through senescence. Though a complete picture has yet to emerge, it is clear that epigenetic changes to the genome promote a range of proce...
We have previously shown in infant rats that brief and repeated experiences with a stressed dam outside the homecage (maltreatment) alters methylation of DNA associated with the brain-derived neurotrophic factor (bdnf) gene within the developing and adult prefrontal cortex. BDNF is a key mediator of activity-dependent processes that have a profound...
The fifth edition of a work that defines the field of cognitive neuroscience, with entirely new material that reflects recent advances in the field. Each edition of this classic reference has proved to be a benchmark in the developing field of cognitive neuroscience. The fifth edition of The Cognitive Neurosciences continues to chart new directions...
Previous work with various animal models has demonstrated that alterations in the caregiving environment produce long-term changes in anxiety-related and social behaviors, as well as amygdala gene expression. We previously introduced a rodent model in which the timing and duration of exposure to maltreatment or nurturing care outside the home cage...
Following adverse childhood experiences, high quality maternal care can protect against accelerated telomere shortening in peripheral cells. It is less clear, however, how telomere length in the brain is influenced by early caregiving experiences. Using rats, we investigated if quality of care (i.e., aversive or nurturing care outside of the homeca...
In the past decade, there have been exciting advances in the field of behavioral epigenetics that have provided new insights into a biological basis of neural and behavioral effects of gene-environment interactions. It is now understood that changes in the activity of genes established through epigenetic alterations occur as a consequence of exposu...
Quality of maternal care experienced during infancy is a key factor that can confer vulnerability or resilience to psychiatric disorders later in life. Research continues to indicate that early-life experiences can affect developmental trajectories through epigenetic alterations capable of affecting gene regulation and neural plasticity. Previously...
Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment...
Quality of maternal care in infancy is an important contributing factor in the development of behavior and psychopathology. One way maternal care could affect behavioral trajectories is through environmentally induced epigenetic alterations within brain regions known to play prominent roles in cognition, emotion regulation, and stress responsivity....
Early-life stress, such as maltreatment, institutionalization, and exposure to violence, is associated with accelerated telomere shortening. Telomere shortening may thus represent a biomarker of early adversity. Previous studies have suggested that responsive parenting may protect children from the negative biological and behavioral consequences of...
Recent discoveries have associated epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA (miRNA) processing, with activity-dependent changes in gene expression necessary to drive long-term memory formation. Here, we discuss the current interpretation of epigenetic mechanisms in the context of memory and sustained beh...
Rationale/statement of the problem : There is an insufficient understanding of the neurobiology of post-traumatic stress disorder (PTSD). Therefore, the development of an animal model of PTSD that takes into account clinical features of the disorder is of value toward enhancing our understanding of the mechanisms, and in the development of novel tr...
Gene-environment interactions have long been recognized for their important role in mediating the development and functions of the central nervous system (CNS). The study of DNA methylation and histone modifications, biochemical processes collectively referred to as epigenetic mechanisms, is helping to elucidate how gene-environmental interactions...
Rationale/statement of the problem : Childhood maltreatment negatively impacts brain development, often producing transgenerational continuity of abusive parenting and increased risk for a range of psychiatric disorders. The biological basis for these far-reaching effects is not currently understood, but evidence suggests traumatic events could aff...
This chapter discusses the epigenetics of memory processes. Epigenetic mechanisms have some necessary role in the dynamic nature of the adult CNS in response to the environment, and that epigenetic regulation of gene transcription facilitates memory formation. Studies also indicate that manipulation of such mechanisms can restore learning and memor...
Experiences during early development profoundly affect development of the central nervous system (CNS) to impart either risk for or resilience to later psychopathology. Work in the developmental neuroscience field is providing compelling data that epigenetic marking of the genome may underlie aspects of this process. Experiments in rodents continue...
Studies over the past half-century have made it clear that environmental influences in development, particularly stress and traumatic experiences, can remain pervasive across the lifespan. Though it has been hypothesized for some time that the long-term consequences of early-life adversity represent epigenetic influences, it has not been until rece...
Here we review the neurobiology of infant odor learning in rats, and discuss the unique role of the stress hormone corticosterone (CORT) in the learning necessary for the developing rat. During the first 9 postnatal (PN) days, infants readily learn odor preferences, while aversion and fear learning are attenuated. Such restricted learning may ensur...
Infant rats must learn to identify their mother's diet-dependent odor. Once learned, maternal odor controls pups' approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonata...
Rapid advances in the field of epigenetics are revealing a new way to understand how we can form and store strong memories of significant events in our lives. Epigenetic modifications of chromatin, namely the post-translational modifications of nuclear proteins and covalent modification of DNA that regulate gene activity in the CNS (central nervous...
This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin stru...
The transcription of genes that support memory processes are likely to be impacted by the normal aging process. Because Arc is necessary for memory consolidation and enduring synaptic plasticity, we examined Arc transcription within the aged hippocampus. Here, we report that Arc transcription is reduced within the aged hippocampus compared to the a...
The fourth edition of the work that defines the field of cognitive neuroscience, offering completely new material. Each edition of this classic reference has proved to be a benchmark in the developing field of cognitive neuroscience. The fourth edition of The Cognitive Neurosciences continues to chart new directions in the study of the biologic und...
This brief review focuses on the role of epigenetic mechanisms in plasticity and memory formation, and their identification as targets of activity-dependent regulation in neurons. Epigenetic modifications of chromatin, namely post-translational modifications of nuclear proteins and covalent modification of DNA, result in potent regulation of gene r...
Epidemiological research suggests that both an individual's genes and the environment underlie the pathophysiology of schizophrenia. Molecular mechanisms mediating the interplay between genes and the environment are likely to have a significant role in the onset of the disorder. Recent work indicates that epigenetic mechanisms, or the chemical mark...
Childhood maltreatment and early trauma leave lasting imprints on neural mechanisms of cognition and emotion. With a rat model of infant maltreatment by a caregiver, we investigated whether early-life adversity leaves lasting epigenetic marks at the brain-derived neurotrophic factor (BDNF) gene in the central nervous system.
During the first postna...
Long-term memory formation requires selective changes in gene expression. Here, we determined the contribution of chromatin remodeling to learning-induced changes in brain-derived neurotrophic factor (bdnf) gene expression in the adult hippocampus. Contextual fear learning induced differential regulation of exon-specific bdnf mRNAs (I, IV, VI, IX)...
Mitogen-activated Protein Kinases (MAPKs) are critical for the formation of stable long-term memories. New work shows that circadian MAPK activity cycling is important in the formation of new hippocampus-dependent memories.
Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a...
Paradoxically, fear conditioning (odor-0.5 mA shock) yields a learned odor preference in the neonate, presumably due to a unique learning and memory circuit that does not include apparent amygdala participation. Post-training opioid antagonism with naltrexone (NTX) blocks consolidation of this odor preference and instead yields memory of a learned...
DNA (cytosine-5) methylation represents one of the most widely used mechanisms of enduring cellular memory. Stable patterns of DNA methylation are established during development, resulting in creation of persisting cellular phenotypes. There is growing evidence that the nervous system has co-opted a number of cellular mechanisms used during develop...
This chapter explores some of the molecular events contributing to memory formation and how, when these events malfunction, disturbances in memory occur. After a brief discussion of signaling in the hippocampus, we will explore the topics of human mental retardation syndromes that involve disruption of these processes, including Angelman syndrome (...
Infant neurobehavioral development is profoundly affected by experiences associated with caregiver attachment. Given the impact that early childhood experience has on neurobehavioral development, there has been little investigation into the cellular and molecular mechanisms responsible for experience-induced developmental changes and particularly h...
Maternal touch profoundly regulates infant neural and behavioral development, and supports learned odor associations necessary for infant attachment. Endogenous opioids are well characterized to mediate the calming and analgesic properties of maternal touch; yet their role in learned odor-touch associations is unknown. We administered naltrexone, a...
While children form an attachment to their abusive caregiver, they are susceptible to mental illness and brain abnormalities. To understand this important clinical issue, we have developed a rat animal model of abusive attachment where odor paired with shock paradoxically produces an odor preference. Here, we extend this model to a seminaturalistic...
There are three notable take-home messages. First, neonatal learning has unique characteristics that seem to ensure that the infant will attach to its caregiver. These characteristics include rapid and persistent seeking of proximity to the caregiver, and remaining attached to the caregiver despite abusive behavior. This basic phenomenon of the inf...
In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and incre...
To support nipple attachment and huddling, rat pups must learn to approach and prefer maternal odor. Similar to other altricial species, rat pups have a sensitive period for learning this odor preference, which ends around postnatal day (PN) 10 and coincides with the emergence of walking. One characteristic of this sensitive period is that an odor...
We assessed the neurochemical basis of olfactory learning induced by presentations of odor and moderate shock in infant rats. Paradoxically, shock conditioning produces an odor preference in 8-day-olds, but an odor aversion in 12-day-olds. Studies have demonstrated the importance of opioids in early olfactory learning; their specific role remains u...
