Laurie L Wellman

Laurie L Wellman
Eastern Virginia Medical School | EVMS · Department of Pathology and Anatomy

PhD

About

90
Publications
4,504
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
893
Citations
Citations since 2017
44 Research Items
521 Citations
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
Additional affiliations
October 2010 - July 2015
Eastern Virginia Medical School
Position
  • Professor (Assistant)

Publications

Publications (90)
Article
Full-text available
Chronic sleep disturbances (CSDs) including insomnia, insufficient sleep time, and poor sleep quality are major public health concerns around the world, especially in developed countries. CSDs are major health risk factors linked to multiple neurodegenerative and neuropsychological diseases. It has been suggested that CSDs could activate microglia...
Chapter
Telemetry can be a powerful tool for assessing physiological responses to emotional stimuli. It can provide continuously recorded data over the course of the stress response and can be incorporated into established behavioral paradigms and procedures in a relatively seamless fashion. Our lab has been using telemetry in conjunction with behavioral p...
Article
Full-text available
Stress induces neuroinflammation and disrupts sleep, which together can promote a number of stress-related disorders. Fear memories associated with stress can resurface and reproduce symptoms. Our previous studies have demonstrated sleep outcomes can be modified by stressor controllability following stress and fear memory recall. However, it is unk...
Article
Full-text available
Sleep disorders have high comorbidity with drug addiction and function as major risk factors for developing drug addiction. Recent studies have indicated that both sleep disturbance (SD) and abused drugs could activate microglia, and that increased neuroinflammation plays a critical role in the pathogenesis of both diseases. Whether microglia are i...
Article
Atherosclerosis is a chronic inflammatory disease of large and medium size vessels that progresses across a lifespan and has been extensively linked to insufficient sleep. Poor fragmented sleep quality is strongly associated with all-cause mortality. Accumulating evidence demonstrates the independent effects of atherosclerosis and fragmented sleep...
Article
Given the growing prevalence of Alzheimer's disease (AD), we assessed the impact of virtually embodying someone with progressive AD. This pilot explored students' understanding of individuals' needs with dementia, as well as, the efficacy of virtual reality (VR) as a curricular tool. Second-year medical students (n = 150) completed a pre-survey, Em...
Article
The central nucleus of the amygdala (CNA) projects to brainstem regions that generate and regulate rapid eye movement sleep (REM). We used optogenetics to assess the influence of CNA inputs into reticularis pontis oralis (RPO), pedunculopontine tegmentum (PPT) and nucleus subcoeruleus (SubC) on dark period sleep. We compared these results to effect...
Chapter
Optogenetics, a method of inducing expression and subsequent activation or inhibition of light sensitive ion channels, allows selective and precise spatial and temporal manipulation of neurons. It is a powerful tool for examining neural circuits regulating sleep and arousal, and how they interact with other systems. This chapter discusses some of i...
Article
Full-text available
The basolateral amygdala (BLA) mediates the effects of stress and fear on rapid eye movement sleep (REM) and on REM-related theta (θ) oscillatory activity in the electroencephalograph (EEG), which is implicated in fear memory consolidation. We used optogenetics to assess the potential role of BLA glutamate neurons (BLAGlu) in regulating behavioral,...
Article
Full-text available
Bi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota–gut–brain axis. Male C57BL/6NCrl mice (4 to 5 per cage, fed sta...
Article
Full-text available
In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity t...
Article
Full-text available
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional i...
Article
Pharmacological and optogenetic studies have demonstrated that the basolateral amygdala (BLA) plays a pivotal role in regulating fear-conditioned changes in sleep, in particular, rapid eye movement sleep (REM). However, the linkage between BLA and REM regulation has been minimally examined. In this study, we optogenetically activated or inhibited B...
Article
Full-text available
Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator...
Article
Ground-based rodent models have established that space radiation doses (approximately those that astronauts will be exposed to on a mission to Mars) significantly impair performance in a wide range of cognitive tasks. Over the last 40 years there has been a progressive increase in both the complexity and the translatability (to humans) of the cogni...
Article
We examined the role of miR146a, a predicted negative regulator of innate immunity, in regulating the effects of stressor controllability on the neuroimmune response to vesicular stomatitis virus. Brain innate immune responses in wild-type and miR146a-/-mice subjected to controllable or uncontrollable stress were characterized. miR146a-/-mice had d...
Article
Astronauts on deep space missions will be required to work autonomously and thus their ability to perform executive functions could be critical to mission success. Ground-based rodent experiments have shown that low (<25 cGy) doses of several space radiation (SR) ions impair various aspects of executive function. Translating ground-based rodent stu...
Article
Group II metabotropic glutamate receptors (mGluR2/3 s) have been implicated in stress and trauma related disorders including post-traumatic stress disorder (PTSD). PTSD is characterized by flashbacks, anxiety, and sleep disturbances. While many people are exposed to trauma in their lifetime, only a small percentage go on to develop PTSD, indicating...
Article
There are roughly 70 million Americans who report insufficient sleep due to work responsibilities, sleep apnea, or lifestyle choices. Altered duration and poor sleep quality are associated with an increase in brain inflammation, high rates of cardiovascular disease and other inflammatory diseases in humans. It is known that psychological stress is...
Article
Purpose: Astronauts on the planned missions to Mars are expected to have to work more autonomously than on previous missions. Thus mission success may be influenced by the astronauts’ ability to respond quickly to unexpected problems, processes that require several executive functions. The purpose of this study was to determine the impact that prol...
Article
Study Objectives To examine the REM sleep response to mild stress as a predictor of the REM response to intense stress and brain-derived neurotrophic factor (BDNF) as a potential biomarker of stress resilience and vulnerability. Methods Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG and intraperitoneal Data...
Article
Study Objectives Sleep, in particular rapid eye movement (REM), has been linked to fear learning and extinction; however, their relationship is poorly understood. We determined how different delays of extinction training (ET) impact fear-conditioned behaviors, changes in sleep, and stress responses. Methods EEG activity, movement, and body tempera...
Article
Sleep fragmentation (SF) is tightly correlated with the development of chronic low grade inflammatory diseases such as, type 2 diabetes and atherosclerosis; however, the exact relationship between SF and atherogenesis is unknown. Little evidence exists regarding the origin of sex differences in sleep behavior. While the role of gender has been stud...
Article
Introduction Post-traumatic stress disorder (PTSD) affects approximately 24 million people in America, and sleep disturbances are the primary symptoms. However, only approximately 20% of individuals exposed to trauma develop chronic problems with sleep indicating individual differences in stress-induced sleep changes. Currently, no methods exist to...
Article
Introduction Pharmacological and optogenetic studies have demonstrated that the basolateral amygdala (BLA) plays a pivotal role in regulating fear-conditioned changes in sleep, in particular, rapid eye movement sleep (REM). However, the linkage between BLA and REM regulation has been minimally examined. In this study, we optogenetically activated o...
Chapter
Intense stress has the potential to produce traumatic memories that are core features of chronic mental disorders. However, encountering even intense stress most often does not have a persisting negative impact on health. Stress outcomes appear to involve complex interactions of sleep, learning, stressor qualities, and individual differences in res...
Article
Full-text available
Introduction: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor-infiltrating lymphocytes (TILs) [CD3⁺, CD4⁺, and CD8⁺ TILs] are potential prognostic indicators in PCa, and variations may contribute to racial disparities in tumor biology and PCa outcome...
Article
Atherosclerosis is a chronic, inflammatory disease characterized by the hardening and narrowing of the small and medium sized arteries caused by the accumulation of fatty plaque lesions. In the USA, approximately 30% of the population reports insufficient sleep, and nearly 70 million people have a diagnosed sleep disorder. Chronic sleep fragmentati...
Article
The basolateral nucleus of the amygdala (BLA) plays a significant role in mediating individual differences in the effects of fear memory on sleep. Here, we assessed the effects of antagonizing corticotropin releasing factor receptor 1 (CRFR1) after shock training (ST) on fear-conditioned behaviors and sleep. Outbred Wistar rats were surgically impl...
Article
Intranasal instillation of vesicular stomatitis virus (VSV) into mice given controllable stress (modeled by escapable foot shock, ES) resulted in enhanced pathogenicity and decreased survival relative to infected mice given uncontrollable stress (modeled by inescapable foot shock, IS) and non-shocked control mice. Survival likely reflected differen...
Article
Introduction Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CTX) alone can produce significant fear indicated by increased freezing, a stress response, and alterations in subsequent REM sleep. These alterations may vary amongst animals and are mediated by the basolateral nucleus of the amygdala (B...
Article
Introduction The central nucleus of the amygdala (CNA) projects to brainstem regions that generate and regulate REM. However, synaptic mapping of the circuitry and the actual influence of the CNA on these regions has not been determined. In this study, we used optogenetic methods to assess the influence of CNA inputs into the oral pontine reticular...
Article
Introduction Bi-directional interactions between the gut microbiota, immune system, and brain (microbiota-gut-brain (M-G-B) axis) are thought to be critical mediators of health and disease. Here, we assessed the effects of sleep fragmentation (SF) on the M-G-B axis. Methods Mice (4 to 5 per cage) were housed in devices (Lafayette Instruments, Slee...
Article
Introduction The amygdala, via the CNA, has direct projections to the LC and other regions (e.g., LDT, PPT, DRN, and subcoeruleus) in the mesopontine brainstem that play significant roles in regulating both sleep and arousal and the stress response. Here we used optogenetics to assess how CNA regulates neural activity in LC in anesthetized rats. M...
Article
The amygdala is an integrator of affective processing, and a key component of a network regulating social behavior. While decades of lesion studies in nonhuman primates have shown alterations in social interactions after amygdala damage, acute manipulations of the amygdala in primates have been underexplored. We recently reported (Wellman, Forcelli...
Article
Full-text available
Study Objectives Stressful events can directly produce significant alterations in subsequent sleep, in particular, rapid eye movement sleep (REM); however, the neural mechanisms underlying the process are not fully known. Here, we investigated the role of the basolateral nuclei of the amygdala (BLA) in regulating the effects of stressful experience...
Chapter
Full-text available
Stress-induced alterations in sleep have been linked to the development of post-traumatic stress disorder (PTSD) and sleep complaints and disturbances in arousal are continuing symptoms in patients. PTSD-related changes in sleep have not been fully characterized but involve persistent disturbances in both rapid eye movement sleep (REMS) and non-rap...
Article
Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CR) alone can produce significant behavioral fear, a stress response and alterations in subsequent REM sleep. These alterations may vary among animals and are mediated by the basolateral nucleus of the amygdala (BLA). Here, we used the GABAA agonist,...
Article
Full-text available
Both hypoactivity and hyperactivity in the amygdala are associated with perturbations in social behavior. While >60 years of experimental manipulations of the amygdala in animal models have shown that amygdala is critical for social behavior, many of these studies contradict one another. Moreover, several questions remain unaddressed. (1) What effe...
Article
Full-text available
Brain circuitry underlying defensive behaviors includes forebrain modulatory sites, e.g., the amygdala and hypothalamus, and midbrain effector regions, such as the deep/intermediate layers of the superior colliculus (DLSC). When disinhibited, this network biases behavior towards reflexive defense reactions. While well characterized in rodent models...
Article
Intranasal application of neurotropic vesicular stomatitis virus (VSV) replicates in olfactory receptor neurons and then rapidly invades the olfactory bulb (OB). VSV has an established time course of progression through discrete brain regions and of onset and recovery from encephalitis. Coincident with viral progression is a bimodal brain cytokine...
Article
Study objectives: To examine the REM sleep response to stress and fearful memories as a potential marker of stress resilience and vulnerability and to assess the role of the basolateral amygdala (BLA) in mediating the effects of fear memory on sleep. Methods: Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG...
Article
Full-text available
Corticotropin releasing factor (CRF) is a major mediator of central nervous system responses to stressors, including alterations in wakefulness and sleep. However, its role in mediating stress-induced alterations in sleep has not been fully delineated. In this study, we assessed the role of CRF and the non-specific CRF antagonist, astressin (AST),...
Article
Vesicular stomatitis virus (VSV) applied intranasally produces a well-characterized encephalitis. However, mice that experienced controllable stress via an escapable foot-shock (ES) demonstrated an enhanced immune response relative to mice that experienced uncontrollable stress (inescapable foot shock, IS) or non-stressed control mice (NS). These d...
Article
Real time sensing of localized electrophysiological and neurochemical signals associated with spontaneous and evoked neural activity is critically important for understanding neural networks in the brain. Our goal is to enhance the functionality and flexibility of a neural sensing and stimulation system for the observation of brain activity that wi...
Article
The perirhinal cortex (PRc) is essential for visual recognition memory, as shown by electrophysiological recordings and lesion studies in a variety of species. However, relatively little is known about the functional contributions of perirhinal subregions. Here we used a systematic mapping approach to identify the critical subregions of PRc through...
Article
Fear conditioning [inescapable shock training (ST)] and fearful context re-exposure (CR) alone can produce significant fear indicated by increased freezing and reductions in subsequent rapid eye movement (REM) sleep. Damage to or inactivation of the basolateral nucleus of the amygdala (BLA) prior to or after ST or prior to CR generally has been fou...
Conference Paper
In this research, chronic sensing parameters and an animal protocol for recording sleep-related changes in glutamate in the basolateral amygdala (BLA) were examined and verified. For chronic sensing, glutamate concentration was measured in rat BLA in real time by an enzyme electrode. In order to analyze the correlation of glutamate level with sleep...
Article
Intranasal application of vesicular stomatitis virus (VSV) produces a well-characterized model of viral encephalitis in mice. Within one day post-infection (PI), VSV travels to the olfactory bulb and, over the course of 7 days, it infects regions and tracts extending into the brainstem followed by clearance and recovery in most mice by PI day 14 (P...
Article
To determine whether corticotropin-releasing factor (CRF) in the basolateral amygdala (BLA) modulated sleep and fear-conditioned alterations in sleep. After 2 days of habituation to recording procedures, baseline sleep recordings were obtained. The animals were then habituated to the handling procedure necessary for microinjections over 2 consecuti...
Article
Full-text available
Controllable stress, modeled by escapable shock (ES), can produce significant alterations in post-stress sleep, including increased rapid eye movement (REM) sleep. Recent work has demonstrated that post-stress sleep may be influenced by stressor predictability, modeled by predictive auditory cues. In this study, we trained mice with ES, either sign...
Article
Stimulation of the intermediate and deep layers of superior colliculus (DLSC) in rodents evokes both orienting/pursuit (approach) and avoidance/flight (defense) responses (Dean et al., 1989). These two classes of response are subserved by distinct output projections associated with lateral (approach) and medial (defense) DLSC (Comoli et al., 2012)....
Article
Stress can have a significant negative impact on health and stress-induced alterations in sleep are implicated in both human sleep disorders and in psychiatric disorders in which sleep is affected. We have demonstrated that the amygdala, a region critical for regulating emotion, is a key modulator of sleep. Our current research is focused on unders...
Article
Systemic administration of the Group II metabotropic glutamate (mGlu) receptor agonist, LY379268 (LY37), dose-dependently suppresses rapid eye movement sleep (REM) whereas systemic administration of the mGlu II receptor antagonist, LY341495 (LY34), increases arousal. Group II mGlu receptors are highly expressed in the amygdala, a brain region invol...
Article
Full-text available
Contextual fear is followed by significant reductions in rapid eye movement sleep (REM) that are regulated by the central nucleus of the amygdala (CNA). Corticotropin-releasing factor (CRF) plays a major role in regulating the stress response as well as arousal, and CRF in CNA is implicated in stress-related behavior. To test the hypothesis that CR...
Article
Telemetry in mice can be a powerful tool for assessing physiological responses to emotional stimuli. It can provide continuously recorded data over the course of the stress response and can be incorporated into established behavioral paradigms and procedures in a relatively seamless fashion. Our lab has been using telemetry in conjunction with beha...
Article
Full-text available
Predictability and controllability are important factors in the persisting effects of stress. We trained mice with signaled, escapable shock (SES) and with signaled, inescapable shock (SIS) to determine whether shock predictability can be a significant factor in the effects of stress on sleep. Male BALB/cJ mice were implanted with transmitters for...
Article
Rapid eye movement sleep (REM) is increased after controllable stress (modeled by escapable footshock, ES) and decreased after uncontrollable stress (modeled by inescapable footshock, IS). Decreases in REM after IS are exacerbated by corticotropin releasing factor (CRF) and attenuated by a CRF antagonist. In this study, we trained mice with ES foll...
Data
Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain,...
Article
Full-text available
Inescapable shock (IS), an uncontrollable stressor, and presentation of fearful contexts associated with IS produce prominent reductions in REM sleep. We compared sleep in animals trained with IS to that in animals trained with escapable shock (ES), a controllable stressor, in a paradigm in which animals always received shock but could terminate it...
Article
Full-text available
Rapid eye movement sleep (REM) appears to be especially susceptible to the effects of stress; inescapable footshock stress (IS) can produce reductions in REM that can occur without recovery sleep. The amygdala has well-established roles in stress and emotion; the central nucleus of the amygdala (CNA) projects to REM regulatory regions in the brains...
Article
Contextual fear significantly reduces rapid eye movement sleep (REM) during post-exposure sleep in mice and rats. Corticotropin releasing factor (CRF) plays a major role in CNS responses to stressors. We examined the influence of CRF and astressin (AST), a non-specific CRF antagonist, on sleep after contextual fear in BALB/c mice. Male mice were im...