United States

Alcohol exposure (AE) during pregnancy is known to affect fetal medial prefrontal cortex (mPFC) and hippocampus (HC) development. Previous work has demonstrated that these two structures are vulnerable to AE during the brain growth spurt, which occurs during 3rd trimester of human pregnancy and the first two postnatal weeks in rodents. Our lab has shown that thalamic nucleus reuniens (Re) is damaged in a rodent model of human 3rd trimester AE. We have also shown that Re is critical for mPFC–HC oscillatory synchrony and spatial working memory (SWM). The current study investigated the effects of early AE on SWM ability in adulthood in rats. We predicted that AE would lead to SWM impairment that worsened as working memory demand increased. We administered 5.25 g/kg/day of ethanol in milk formula via intragastric intubations in a binge manner on PD 4-9 (AE group) or performed intubations without liquid (sham intubated (SI) group). On PD90, rats were trained on a continuous alternation (CA) T-maze task. Upon reaching a choice accuracy criterion of 80% for two consecutive days on CA, we introduced a delay between trials (DA) in order to increase SWM demand. The rats underwent 6 DA sessions, consisting of 12 each of 10-second (s), 30 s, and 60 s delay trials given in a pseudorandom sequence. Our results show that animals in both AE and SI groups learned the CA task at similar rates. However, on the DA task, the SI group showed consistent improvement across sessions on the 30-s delay trials, whereas the AE group did not (postnatal - treatment x day interaction: F(5,195)=2.70, p = .02). For the 10 s delay trials, both AE and SI groups showed improvement across days (main effect of day: F(5,195)=7.93 , p &lt; .001), whereas for the 60 s delay trials, both groups performed uniformly poorly across days. These findings support the hypothesis that binge AE during the brain growth spurt produces SWM deficits that depend on SWM demand. This study will lead to a better understanding of the impact of HC-Re-mPFC circuitry damage due to developmental AE on cognitive function later in life.

Delaware Neuroscience Symposium 2021

Delay-dependent spatial working memory deficits in a rat model of third trimester alcohol exposure.

Welcome Seabirders!  

Welcome to Virtual World Seabird Conference 3 - vWSC3! Whether you are in your office or lab, at home, in a coffee shop or bar poaching some wifi, or at a remote field site or research vessel – we are very excited to welcome you to the third ever World Seabird Conference. 

We would like to thank ALL of you for being so patient as WSC3 was scheduled, postponed, rescheduled, revised to virtual, and scheduled again. Throughout all those iterations there was one message that remained perfectly clear – seabirders were eager to meet and share their science. If we could not meet in person then virtual it would have to be, but a 3rd WSC was something everyone wanted. That support and commitment helped the WSU Board of Directors and Member Societies sort through all of the challenges they faced to plan and hold this conference. 

The list of those that need to be thanked is long and, while we plan on recognizing many during the live closing plenary, it is important to do so here in writing as well. 

The Australasian Seabird Group was our Local Host for our plan to meet in Hobart, Tasmania. They invested substantial time and effort to find venues and plan events that we unfortunately were not able to visit. Nonetheless we appreciate their work on behalf of WSC3 and encourage all of you to thank them when you see their members in Gathertown or elsewhere during our virtual meeting. Their willingness to host created the initial excitement for WSC3 and without that our vWSC would not have been possible.

We also wish to thank the Science Program Committee, the Virtual Committee, and the Early Career Scientist Committee for their hard work planning the logistics, events, and schedule for vWSC3. These committees also had to deal with changing parameters and short timelines that made what is always a challenging task even more challenging. The Travel Awards Committee also invested time and effort in developing procedures for awarding travel funds that ultimately would not be implemented. 

Our ability to shift from an in-person to a virtual meeting, and to do so in a way that would be financially feasible, was due to the effective efforts of The International Fundraising Committee and to our financial sponsors. The IFC raised funds to support WSC3 and then, through the good relationships they built with sponsors, ensured we could re-envision how those funds could be used to support a virtual conference that would be affordable and high-quality.

We all owe the WSU Board of Directors and the Representatives of the Member Societies a great deal of thanks. They are the ones who manage the WSU and, for the past 18 months, have had to have a series of challenging meetings and conversations, have had to make a series of difficult choices, have had to do all of that while considering the short- and long-term health of WSU and the World Seabird Conferences, and did this while also managing their own challenges at their day jobs. We are grateful for their diligence, patience, foresight, and throughout all of the meetings, their collegiality. Also – a 6-year term is quite a commitment!

There would not be a WSC3 without a successful WSC1 and WSC2. Thanks go to the Pacific Seabird Group for their support of WSC1 in Victoria, Canada, and to the African Seabird Group for their support of WSC2 in Cape Town, South Africa. In each of these endeavors and for our current conference we were fortunate to work with a dependable and trustworthy partner in Podium Conferences. Michelle Smith and Marischal de Armond have become valued members of our team and have not only helped us plan conferences but have assisted and advised the WSU Chairs and Board on issues above and beyond conference planning. 

As we embark on our vWSC3 week we extend to all of you our thanks for showing up, for being patient, and most importantly for the work you do with seabirds. We are all part of a unique, global community that shares an interest, a fascination, and a passion for birds that make a living in our world’s oceans. We have advanced the science, conservation, and management of seabirds as well the ecosystems they inhabit. We are consistently impressed and motivated by the work you do. 

The WSU formed in 2010 because we saw the need for a global organization to address challenges at a global level. Over the past 11 years WSU has grown, adapted, and evolved to become the community that this week is making vWSC3 a reality. Enjoy the week, appreciate and support the friends and colleagues you have made in the community, and if you see us in a virtual hallway please stop and say hello! 

Thank you for the opportunity to serve all of you and the WSU over the past few years,

Nicholas Carlile, Interim Chair, WSU<br>
Patrick Jodice, 2nd Chair of the WSU<br><br>

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3rd World Seabird Conference

Join us for four days of science, networking and virtual engagement with delegates from around the world!

Alcohol exposure (AE) during pregnancy is known to affect fetal medial prefrontal cortex (mPFC) and hippocampus (HC) development. Previous work has demonstrated that these two structures are vulnerable to AE during the brain growth spurt, which occurs during 3rd trimester of human pregnancy and the first two postnatal weeks in rodents. Our lab has shown that thalamic nucleus reuniens (Re) is damaged in a rodent model of human 3rd trimester AE. We have also shown that Re is critical for mPFC–HC oscillatory synchrony and spatial working memory (SWM). The current study investigated the effects of early AE on SWM ability in adulthood in rats. We predicted that AE would lead to SWM impairment that worsened as working memory demand increased. We administered 5.25 g/kg/day of ethanol in milk formula via intragastric intubations in a binge manner on PD 4-9 (AE group) or performed intubations without liquid (sham intubated (SI) group). On PD90, rats were trained on a continuous alternation (CA) T-maze task. Upon reaching a choice accuracy criterion of 80% for two consecutive days on CA, we introduced a delay between trials (DA) in order to increase SWM demand. The rats underwent 6 DA sessions, consisting of 12 each of 10-second (s), 30 s, and 60 s delay trials given in a pseudorandom sequence. Our results show that animals in both AE and SI groups learned the CA task at similar rates. However, on the DA task, the SI group showed consistent improvement across sessions on the 30-s delay trials, whereas the AE group did not (postnatal - treatment x day interaction: F(5,195)=2.70, p = .02). For the 10 s delay trials, both AE and SI groups showed improvement across days (main effect of day: F(5,195)=7.93 , p < .001), whereas for the 60 s delay trials, both groups performed uniformly poorly across days. These findings support the hypothesis that binge AE during the brain growth spurt produces SWM deficits that depend on SWM demand. This study will lead to a better understanding of the impact of HC-Re-mPFC circuitry damage due to developmental AE on cognitive function later in life.

technical paper

This annual event showcases and celebrates the neuroscience research in Delaware.  Posters and talks highlight neuroscience research carried out by graduate students, undergraduate students, and research staff at all of Delaware’s research and education institutions. The Lounge section of the symposium allows real-time interactions and networking among attendees.  New this year is an expo of research core facilities in Delaware.  Check them out in the Research Cores section of our poster session, or see the logos below.

Aversive caregiving in early life is a risk factor for aberrant brain and behavioral development throughout the lifespan. This outcome is related to aberrant epigenetic regulation of the Bdnf gene. The Bdnf gene encodes for brain-derived neurotrophic factor (BDNF), a neurotrophin involved in neural plasticity, learning, and memory. Disruptions in caregiver-infant interactions lead to increased methylation and decreased expression of the Bdnf gene. One way to mitigate this effect is hypothesized to be through aerobic exercise. Exercise increases BDNF at the protein and gene expression levels, making it an exciting target for therapeutic interventions. To our knowledge, exercise has never been studied as a therapeutic intervention in preclinical rodent models of early life maltreatment. To that end, the current study is investigating the effect of an adult voluntary wheel running intervention on Bdnf aberrant methylation and expression in the prefrontal cortex of rats who experienced aversive caregiving in infancy. This study presents novel findings on the mechanisms underlying neural plasticity in the prefrontal cortex in an early life stress context.

Mitigating the Epigenetic Consequences of Early Life Stress with a Behavioral Intervention

In adolescents, low sleep duration is associated with psychiatric disorders, cognitive problems (Cheng et al., 2020), and diminished academic performance (Eliasson et al., 2002). This is particularly problematic for racial and ethnic minority adolescents, who are at increased risk of low sleep duration (Singh et al., 2013). While adolescent racial and ethnic low sleep duration has been linked to socioeconomic status (Gugllelmo et al., 2018), physical activity in girls (Bates et al., 2016), and school engagement (Dunbar, Mirpuri, & Yip, 2017), all four factors have not yet been explored together. The current study aims to understand the physiological impact of stress on sleep, which in turn is expected to impact behavior and development differentially by race and ethnicity. The present study will include participants from the National Institute of Health Adolescent Brain Cognitive Development (ABCD) Study. Resting-state neuroimaging data will be used to explore differences in intrinsic connectivity. The results of the current study have the potential to bring to light protective factors: factors that reduce the effects of stress on sleep.

Sleep Disparities in Adolescents

Individuals with chronic stroke affecting the corticospinal track often show severe motor impairment or paralysis of hand. Functional magnetic resonance imaging (fMRI) studies have shown that this impairment corresponds to in a reduction in bold activity in the lesioned hemisphere. It still unclear whether this reduction of brain activity also correspond to changes in the cortical representation of this body part in the motor cortex or whether this representation is preserved. To explore this issue, two individuals with subcortical stroke and paralysis of the hand were presented with an fMRI experiment in which they were asked to move (or to imagine for the paralyzed hand) each digit of hand following a random sequence. Representation similarity analysis was used to explore whether the pattern of activations across fingers in the motor cortex differed, indicating a maintained representation of the hand, or was similar, indicating damage to this representation. Both individuals showed finger differentiation in the ipsilateral M1 and one individual showed differentiation also in the contralateral hemisphere. These results suggest that the representation of the hand in M1 is maintained in individuals with corticospinal damage despite the complete paralysis of the hand, providing important clinical implications for rehabilitation.

Hand representation in individuals with subcortical stroke

Zika Virus (ZIKV) is a single-stranded RNA flavivirus whose primary vector is the Aedes aegypti mosquito and that became widely recognized during the outbreak in Brazil in 2015. In infected adults, symptoms are typically mild and short-lasting. However, in Brazil during the ZIKV outbreak, researchers reported a 20-fold increase of neonatal microcephaly. This congenital ZIKV infection leads to serious clinical outcomes, including seizures and cognitive developmental delays. Our lab has developed a unique rat model of prenatal ZIKV infection to help elucidate the mechanisms and outcomes of this virus throughout development and adulthood. In this study we assessed the long-term impact of congenital ZIKV infection on motor function, cellular proliferation and survival, and on immune response later in life. We found that these prenatally exposed animals demonstrated motor deficits in a sex specific manner and failed to mount a typical immune response to later-life infection. These results suggest that there are significant later life consequences to congenital ZIKV exposure. Continuation of ZIKV research is imperative to understanding the full spectrum of neurological and immunological consequences ZIKV and to help the children currently affected by ZIKV as well as prepare for future outbreaks.

Effect of Prenatal ZIKV Infection on Later-Life Neurogenesis in the Brain

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects movement. Previous magnetic resonance imaging (MRI) studies in PD focused primarily on identifying the neural correlates of upper extremity dysfunction. Although PD progresses to affect lower extremities, there is still a limited understanding of the brain circuitry underlying lower limb symptoms in PD in part because excessive head motion occurs during leg movements in a supine position affecting the functional MRI signal. Here, 11 PD and 14 controls underwent a functional MRI session during which they performed a visually cued isometric ankle dorsiflexion task at 15% of their maximum voluntary contraction (MVC). PD participants were tested off antiparkinsonian medication and their motor symptoms were measured with the MDS-UPDRS- III. While both groups were able to produce 15% of MVC during the ankle dorsiflexion task (p=0.182), PD had a lower rate of force increase (p=0.003) and force decrease (p=0.002) than controls. The fMRI analysis, revealed a reduction in the blood-oxygen-level-dependent (BOLD) signal during the task in PD compared to controls in the contralateral putamen, internal globus pallidus, and sensorimotor cortex. PD also had decreased motor-related signal in the cerebellum, specifically vermis I-IV and the ipsilateral dorsal dentate nucleus. Importantly, percent signal change in vermis I-IV was negatively correlated in PD with total MDS-UPDRS-III (r=-0.759, p=0.007) and the axial subcore (r=-0.615, p=0.044). A trend towards significance was detected for the correlation with the posture and gait subscore (p=0.054). Collectively, results demonstrate force control deficits during lower limb movements in PD that are related to functional abnormalities within both the basal ganglia- and cerebellar-cortical loops. The correlation analyses suggest that the cerebellum may be an important component of the pathophysiology of the disease. Further testing in a larger cohort is necessary to establish if its reduced activity underlies balance and gait symptoms in PD.

Neural Correlates of Ankle Dorsiflexion Movements in Parkinson's Disease

Novel neuroimaging biomarkers are urgently being sought to characterize early changes to the brain in mild cognitive impairment (MCI), typically a precursor to Alzheimer’s disease (AD). As the hippocampus is a critical site of AD pathogenesis that underlies principal symptoms of memory impairment, numerous studies have utilized multiple imaging modalities to characterize hippocampal integrity. The purpose of this study was to utilize a wide range of neuroimaging techniques to determine which measures were the most sensitive in detecting differences in hippocampal integrity between cognitively healthy older adults (OA) and those with amnestic MCI. We used a multimodal neuroimaging approach consisting of measures of hippocampal viscoelasticity, volume, perfusion, and diffusion – including neurite orientation and dispersion density imaging (NODDI) metrics – resulting in a total of twelve separate measures of hippocampal health. We recruited 23 OA and 7 MCI participants. A binomial logistical regression was performed to establish the effect of the 12 hippocampal measures on the likelihood of an MCI diagnosis. We also assessed the odds ratio as a measure of effect size. The full model correctly classified 92% of cases. Viscoelastic damping ratio (DR) from MRE was 27% higher in the MCI group and was the only significant predictor in differentiating between OA and MCI (p=0.024). The significant relationship between MCI status and DR (B=0.911, S.E.=0.404, after adjusting for age and sex) suggests that for every 0.01 increase in DR, the likelihood of having MCI is 2.49 times higher. No other hippocampal measures were significant predictors in the model, although hippocampal volume was close to approaching significance (p=0.056). Viscoelastic damping ratio of the hippocampus was the only significant predictor of MCI. This suggests that MRE measures of viscoelasticity may provide a unique and highly sensitive biophysical signature of hippocampal health relevant to microstructural changes that are expected to occur in MCI.

Multimodal Characterization of Hippocampal Integrity in Mild Cognitive Impairment: Combining Volumetry, Diffusion, Perfusion, and Viscoelasticity from Magnetic Resonance Imaging

The Biomolecular Core Laboratory (BCL) is located at the Nemours/Alfred I duPont Hospital for Children in Wilmington, Delaware and has been serving the clinical and scientific community for 20 years. This resource laboratory has provided essential services in molecular biology and genetics to clinicians and research scientists at Nemours Children’s Health System and affiliated partner institutions including University of Delaware, Thomas Jefferson College of Medicine, Delaware State University, Wesley College, Delaware Technical Community College, and Christiana Care Health System. Working in close collaboration with our partnering institutions throughout the CTR and IDeA networks, our global mission is to facilitate discoveries that begin at both the basic and translational research levels. The BCL is a collaborative research lab providing support for the development of new research projects as well as mentoring, training, and educational opportunities to staff and students. We offer low-cost, fast-turnaround, high-quality services that are essential to many clinical and hypothesis driven projects. The BCL enables research excellence by offering genomics technologies including sanger sequencing, fragment analysis, nucleic acid isolation, digital PCR, genotyping, copy number analysis, gene expression analysis, as well as access to shared instrumentation. The BCL staff not only provides expertise in project design and data troubleshooting but also offers support for grant applications, budget preparations and manuscripts. The ultimate goal of this laboratory is to provide biomedical investigators with state-of-the-art technical support and clinicians with tools that can help improve pediatric supportive care and/or therapeutic intervention. This poster will present an overview of the services available to the IDeA community.

The Nemours Biomolecular Core Lab: A Resource for Biomedical Research

The OSCAR Imaging Facility at Delaware State University (DSU): a multi-user core facility

The OSCAR Imaging Facility at Delaware State University

The “Delaware Nucleotide Analysis (DNA) Core Center” is a genomics core facility debuting at Delaware State University. The Core offers services for a variety of research focuses including biology, medical, environmental, and agricultural sciences. The core is equipped with instruments covering most DNA and RNA sequencing studies. Services include automated systems for sample library preparation and quality control as well as second generation Illumina sequencer and third generation PacBio sequencer. For members of the DSU community, external academic institutions, and the private sector, the core offers full service and a la carte service options dependent upon client request. The DNA Core also provides workshops and educational training for new users of Core systems in the DSU family and external community.

Launching the DNA Core Center at Delaware State University

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized in part by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although the precise cause of PD is not yet fully understood, environmental factors are known to contribute to the etiology of a vast number of cases. Rotenone, a pesticide that inhibits Complex 1 of the Mitochondrial Electron Transport Chain, is one such toxin. Importantly, there is no known cure for PD and effective treatment options are severely limited both in number and efficacy. We are interested in measuring mitochondrial oxygen consumption rate (OCR) using the Seahorse Analyzer in our in vitro and ex vivo model exposed to mitochondrial stressors (Oligomycin, FCCP, and Rotenone/Antimycin). Once mitochondrial respiration measurements have been optimized, we aim to test whether treatment with dacarbazine, a possible neuroprotective agent, can ameliorate the effects of mitochondrial stress. Here, we present preliminary data on the effect of mitochondrial stressors in fly heads and Schneider cells (S2 cells) and the effect of dacarbazine on OCR in fly heads and S2 cells. In sum, our report shows the effects of toxins in mitochondrial metabolism and the utility of a potential neuroprotective chemical against a model of PD and suggests a possible neuroprotective chemical against the disease.

Delay-dependent spatial working memory deficits in a rat model of third trimester alcohol exposure.

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