
**Presenter:**
Melissa Harrington, Delaware State University

**Bio**:  Dr. Harrington is the director of the NIH-funded Delaware Center for Neuroscience Research, an NIH-funded, virtual center linking neuroscientists at Delaware State University and the University of Delaware. She is also the director of the Delaware Institute for Science & Technology, the first research institute at Delaware State University. She has been at DSU since 2001, when she started as an assistant professor in the biology department. She rose through the ranks and currently serves as the associate vice president for research at DSU.



Welcome, introductions and housekeeping


**Presenter:**
Keren-Happuch Ikechi-Konkwo, Delaware State University

**Bio:**
A senior year, biological sciences major with a minor in Chemistry from Delaware State University who is interested in biochemical research.

**Abstract:**  Acetylcholine (ACh) is one of the most abundant neurotransmitters in a human. It works in both the central and the peripheral nervous systems. In addition to its major role in neuromuscular junctions, ACh functions in memory and cognition in the brain. It is known that many Alzheimer’s disease patients have lower levels of acetylcholine.  RNase H2 is a ribonuclease that removes ribonucleotides from DNA. It is also involved in gene expression. Although the full scope of this enzyme’s role in vivo is not fully known, it is a well-known fact that mutations in the RNase H2 genes in humans causes Aicardi-Gouti’s syndrome (AGS), a severe neurological disorder characterized by abnormal neurology and different types of encephalopathies. C. elegans is a nematode and model organism that has been widely used in biomedical research. Not only are they easy to work with and have quick generation times that allow for efficiency in research, but this organism also share more than 80% of its genes with humans. The purpose of this study was to determine, using the organism C. elegans, the effects of a mutation in the RNase H2 gene on cholinergic neurotransmission and the associated behaviors. RNase H2 S114F mutant worms were examined in time course experiments in the presence of ACh in the medium and their behaviors were compared to those of wild-type worms. The specific behavior I observed were locomotion, pharyngeal pumping, and defecation. I found that the rnh-2 S114F mutation significantly affected all these behaviors in which cholinergic neurotransmission is involved. These results suggest that RNase H2 plays an important role in regulation of cholinergic neurotransmission and associated behaviors in C. elegans.


The role of RNase H2 in regulation of cholinergic neurotransmission in Caenorhabditis elegans


**Presenter:**
Nicholas C Cottam, Delaware State University

**Bio:**
I am from Massachusetts, and I acquired my B.S. in Biochemistry at the University of Southern Indiana. There I discovered my interest for neuroscience and decided to pursue a doctoral degree in it at Delaware State University for the Fall of 2020

**Abstract:**
Proximal Spinal Muscular Atrophy (SMA) is an autosomal recessive disease that affects 1 in every 6,000-10,000 individuals at birth, making it the leading genetic cause in infant mortality. SMA is characterized by motor neuron dysfunction and degeneration in the anterior horn of the spinal cord due to a depletion in ubiquitous survival motor neuron protein (SMN) in motor neurons. SMN protein has been thoroughly investigated due to its determining role in SMA pathology and more roles across the cell continue to be revealed. The motor control regions and brain pathology have been largely unstudied, even when distinct cerebral effects have been detected in SMA-affected brains in the recent literature. Whereas there are helpful treatments for SMA patients, a cure is still unavailable. Thus, to uncover the mysteries surrounding SMA, we investigated the cerebellum using SMNΔ7 mice as a model. With diffusion weighted images (DWI) from magnetic resonance imaging (dMRI) scans and segmentation methods in ITK-SNAP, we acquired volumetric data of the brain. These data show that growth of the cerebellum is significantly hindered in SMA-affected mice as compared to wild type. Furthermore, the cerebellum of P12 mice are differentially affected over other brain regions, despite seeing a decrease in whole brain volume. This is cause for further investigation, and future studies can use the DWI images for anatomical analysis for differences in types of tracts, overall tract connectivity and length, as well as common DWI metrics such as fractional anisotropy. Histological staining can confirm these findings and may reveal other anatomical anomalies. Also, RNA sequencing of the cerebellum can be used to elucidate genomic abnormalities in disease-affected mice.


The Role of the Cerebellum in Spinal Muscular Atrophy Pathology in Mice – Magnetic Resonance Imaging Study


**Presenter:**
Katarzyna D Rosikon, Delaware State University

**Bio:**
Katarzyna Rosikon is graduate student-athlete pursuing her master's degree in Cellular and Molecular Neuroscience at Delaware State University.  She is originally from Poland and performing her research in Dr. Dhillon's Lab. Her research project focuses on understanding the modulatory interactions between dopamine auto-receptor and dopamine transporter in regulating synaptic neurotransmitter levels in C.elegans organism. 

**Abstract:** Apposite functioning of the nervous system requires complex interplay between different neurotransmitters. The mechanisms of neurotransmitter release and clearance are highly controlled processes, whose modulation is precisely controlled through different sets of modulators. Dopamine is a key neurotransmitter involved in executive function, motor control, reinforcement and reward, and its homeostatic dysfunction is implicated in Parkinson’s disease, schizophrenia, and addiction amongst other neuro-pathologies. Key dopamine modulators include pre-synaptic D2 auto-receptors, and the dopamine membrane transporter. Previous studies have revealed the individual role of these modulators in regulation of synaptic dopamine; however, an integrated picture for dopamine homeostasis remains unclear. We are using the Caenorhabditis elegans model to test the hypothesis that functional interactions between individual feedback components from the DOP-2 auto-receptor and the DAT-1 membrane transporter merge to form a complex central hub responsible for modulating synaptic vesicle levels. C. elegans has a well-defined 302-neuron nervous system, with four left-right pairs of dopaminergic neurons: CEPD, CEPV, ADE and PDE, which serves as a clear platform to elucidate interactions between synaptic dopamine modulators. Our experimental approach involves in vivo functional imaging using a switchable optical sensor (SEpHluorin) in FRAP-based assays. SEpHluorin is a pH sensitive fluorescent protein with limited fluorescence inside the acidic environment of synaptic vesicles; however, its bright fluorescence is switched on after vesicle fusion upon exposure to the near neutral pH of the synaptic cleft. We are quantifying dopamine release at individual dopamine synaptic termini using synaptic vesicle fusion rates as a surrogate. Our FRAP recovery data from individual synaptic puncta shows that both DOP-2 auto-receptor and DAT-1 transporter provide inhibitory elements in modulating synaptic vesicle fusion. Our current focus is on measuring synaptic fusion rates of dop-2;dat-1 double-deletion mutants in FRAP experiments. In addition, we are investigating their genetic interaction through behavioral assays, namely, SWIP and mechano-sensory habituation.

A negative feedback modulatory hub for synaptic dopamine levels


**Presenter:**
Andy Lam, University of Delaware

**Bio:**
5th year PhD candidate in Tanis Lab at University of Delaware 

**Abstract:**
Alzheimer’s Disease (AD), the most common cause of dementia, is a multifactorial neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, hyperphosphorylated tau, oxidative stress, and mitochondrial dysfunction. AD risk factors including genetic predisposition and aging cannot be changed, but diet, as a modifiable risk factor for AD, could potentially be targeted to slow disease onset and progression. However, it is challenging to determine which nutrients are neuroprotective in humans due to genetic diversity, the complexity of diets, and indirect effects of gut microbiota. C. elegans have been used extensively to identify and characterize factors that influence Aβ toxicity. Transgenic expression of toxic human Aβ in C. elegans body wall muscles generates time-dependent paralysis and AD-like pathological features including defects in mitochondrial function. We discovered that Aβ-expressing C. elegans fed OP50 E. coli exhibited faster paralysis, lower ATP levels, more mitochondrial fragmentation, and increased reactive oxygen species compared to those on HB101 E. coli. This was not due to differences in macronutrient content, but rather on the availability of vitamin B12. B12 supplementation alleviated mitochondrial fragmentation, bioenergetic defects, and oxidative stress, delaying Aβ-induced paralysis without affecting Aβ accumulation in animals fed OP50. Vitamin B12 did not have an additive effect on animals raised on HB101 indicating that supplementation was only beneficial for animals with mild B12 deficiency. We discovered that the protective effects of vitamin B12 required METR-1 (methionine synthase), suggesting that B12 functions as an enzyme cofactor.  Methionine supplementation eliminated the dietary shift in paralysis, consistent with our model in which the amount of vitamin B12 dependent methionine synthase activity impacts Aβ proteotoxicity. Introducing vitamin B12 at adulthood was beneficial for B12 deficient Aβ animals. In conclusion, our results demonstrate the potential for vitamin B12 as a therapy to target pathogenic features of AD triggered by both aging and proteotoxic stress.


Dietary vitamin B12 impacts amyloid-β proteotoxicity by alleviating oxidative stress and mitochondrial dysfunction


**Presenter:**
Mary Beth Bielicki, University of Delaware

**Bio:**
Mary Beth Bielicki is currently pursuing a Ph.D. in Psychology with a concentration in Behavioral Neuroscience at the University of Delaware. She is a Graduate Research Assistant in Jaclyn Schwarz's neuroimmunology lab. Mary Beth's research focuses on how immune activation during development can impact learning behavior and brain function later in life. She earned her BA in Psychology with a minor in Neuroscience from Gettysburg College. Mary Beth is currently the president of Project Brain Light, a graduate student-led organization at the University of Delaware, which aims to support interest in STEM by providing underrepresented students and populations with interactive experiences in science.

**Abstract**:  Early-life immune activation is linked to increased risk for male-biased developmental disorders such as Autism Spectrum Disorder, ADHD, and Schizophrenia. These disorders are associated with hippocampal deficits in learning and cognition. We have found that immune activation with lipopolysaccharide (LPS; 100ug/ml/kg) on postnatal day (P) 21 produces hippocampal-dependent learning deficits in context fear conditioning from P24-P26, in both male and female rats. This suggests P21-P24 may be a critical window for the ontogeny of spatial learning and requisite formation of its underlying circuits. Connections between medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC), and ventral hippocampus (vHPC) have been implicated in context fear learning. Few studies have examined the effects of immune activation on white matter growth across juvenile development, and its associated behavioral and cognitive implications. Our goal is to use diffusion tensor imaging (DTI) to characterize the effects of LPS immune activation on white matter development across these brain regions underlying context fear learning. Preliminary analyses show that, in non-treated rats, dHPC fractional anisotropy increased across development [main effect of age; F(2,9) = 5.96, p = .031]. In vHPC, fractional anisotropy increased from P16 to P20 (p = .027), which is associated with increased axon density or myelination. On the other hand, radial diffusivity (p = .036) and mean diffusivity (p = .048) increased from P16 to P24 in vHPC, which may be associated with decreased axon density or increased gray matter volume. Overall, these findings suggest that dHPC circuitry may be forming during this period of development. vHPC may be in a transition period where circuits are forming from P16 to P20 but are being refined for the ontogeny of learning at P24. Future studies will examine the effects of P21 LPS immune activation on white matter microstructure at P24 and its implications for context learning.

Funding: This study was funded by a R01MH106553 grant to JMS.




Ex-vivo Diffusion Tensor Imaging to Examine the Development of Circuits Underlying Context Fear Conditioning


**Presenter:**
John Stout, University of Delaware

**Bio:**
As a second year graduate student in Amy Griffins laboratory, I am interested in understanding the neurobiological basis of learning and memory

**Abstract:**
When faced with a difficult decision, we often contemplate the outcomes through a  process called deliberation. In rats, there is considerable evidence that deliberation is  expressed through vicarious trial-and-error (VTE) behaviors, where rats pause and re orient at choice-points. Multiple lines of research have demonstrated that VTEs are  linked to spatial working memory (SWM) tasks. And similar to choice accuracy on SWM  tasks, VTE behaviors are impacted by inactivating the medial prefrontal cortex (mPFC)  or hippocampus (HPC). This information, in combination with demonstrations of  synchronized neural activity during decision-making, have led to the formulation of the  hypothesis that the mPFC and HPC communicate in support of deliberation (Redish,  2016). However, no study has examined the impact of disconnecting the mPFC from  the HPC on VTE behaviors. To this end, we analyzed behavioral and  electrophysiological data from a previously published dataset (Hallock et. al., 2016) that  anatomically disconnected the mPFC and HPC through inactivation of the ventral  midline thalamus. We provide the first experimental evidence that inactivation of the  ventral midline thalamus impaired the ability for deliberations to ‘help’ rats make a  correct choice. This impairment coincided with reduced prefrontal-hippocampal neural  synchronization in the theta band. In effect, our data indicates that the mPFC and HPC  communicate in support of deliberation through ventral midline thalamic connectivity.



Suppression of the ventral midline thalamus impacts successful deliberation


**Presenter:**
Grace McIlvain, University of Delaware

**Bio:**
Grace McIlvain is a 4th year PhD student in Biomedical Engineering at UD, studying brain mechancial properties in children and children with developmental disabilites. 

**Abstract:**
<br>Magnetic resonance elastography (MRE) is a technique capable of creating sensitive maps of brain viscoelastic mechanical properties, which can be used as markers of brain microstructural health and have been extensively studied in neurodegeneration. However, brain mechanical changes during maturation have yet to be comprehensively explored. Here we present preliminary brain mechanical property findings from sixty-four healthy subjects from three age groups: 5-7 years, (N =17), 12-14 years (N=24), and 19-21 years (N=22). We use fast-acquisition OSCILLATE MRE at 1.5 mm resolution to capture displacement data, which is converted to whole-brain maps of viscoelastic shear stiffness (μ) through the non-linear inversion equation. 

We found that whole-brain stiffness was significantly different in the 18-21 group compared to the two younger groups. Average stiffness decreased 7.54% between the 5-7 and 18-21 groups (3.05 vs. 2.82 kPa; p<0.001), with no difference found between the 5-7 and 12-14 age groups (3.05 vs. 3.08 kPa). Notably, we find that mechanical properties do change regionally during maturation. Of the subcortical gray matter structures (SGMs), the thalamus, caudate, pallidum and putamen becoming stiffer with maturation, while the amygdala and hippocampus show no decrease or potentially even an increase in stiffness with age. Interestingly, the four SGMs that decrease in stiffness with age, all are components of brain networks important for procedural learning and locomotion regulation, while the hippocampus and amygdala of the medial temporal lobe and are critical in emotional regulation, decision making, and memory formation. The differential change in mechanical properties may reflect how these functions mature.

Here we present measures of maturational brain mechanical properties that will allow for the compilation of a comprehensive set of standardized, high resolution, brain mechanical property maps for prominent time points during development. These measures are pressingly important to inform future studies investigating the neural basis of neurodevelopmental disorders.


MR Elastography Revels Regional Maturational Related Changes to Brain Viscoelastic Shear Stiffness


**Presenter:**
Ye Shen, University of Delaware

**Bio:**
Ye Shen is a Ph.D. candidate specializing in literacy education in the School of Education at the University of Delaware. Her research uses a multifaceted approach to studying bilingual language and literacy development. She is particularly interested in how reading, writing, and the reading-writing relation develop in both bilingual and second language learners’ first and second languages. 

**Abstract:**
Orthographic depth, the degree of the consistency and complexity of grapheme-phoneme correspondence, has been found to influence brain activation in both first (L1) and second language (L2) learning. Using resting-state fMRI, we investigated individual differences in functional connectivity between two groups of bilinguals, those whose L2 orthography is deeper than their L1 and those whose L2 orthography is shallower than their L1. We focused on two key regions of interest, the visual word form area (VWFA) and the left posterior supramarginal gyrus (pSMG), as their respective roles in orthographic processing and cross-language lexical equivalents is well-established. Stronger functional connectivity was observed when orthography was shallower in the L2 than the L1 between the VWFA and the precuneus, as well as between the left pSMG and the precuneus and cingulate gyrus, the right hemisphere supramarginal gyrus and angular gyrus, and the right hemisphere middle frontal gyrus and frontal pole. In contrast, deeper L2 bilinguals showed stronger functional connectivity between the left pSMG and the posterior and temporo-occipital portions of the left middle temporal gyrus, and the left middle frontal gyrus. Further, when comparing L2 and L1 orthographic depth differences between bilinguals and multilinguals, connectivity differences were found between the left pSMG and the left anterior temporal fusiform and the right temporal pole. Thus, pSMG connectivity reflects both orthographic depth and multilingualism. Together, the findings suggest that the brain is functionally “wired” differently depending on the orthographic depth of L2 in relation to L1.


Intrinsic Brain Connectivity Is Shaped by Orthographic Depth of Languages


**Introduction**:  Melissa Harrington, Delaware State University

**Presenter:**
Dr. Jaclyn Schwarz, University of Delaware

![](https://assets.underline.io/uploads/markdown_image/1/image/34cf2a74a57facbca55dec590a8b1d23.jpg)

<br>**Title of talk:**  Effect of early-life immune activation on the ontogeny of learning:  Importance for understanding the etiology of neurodevelopmental disorders

**Bio:** Dr. Schwarz received her PhD from the University of Maryland School of Medicine in 2008 where she studied the mechanisms of brain sexual differentiation. After, she was an NIH-funded postdoctoral fellow at Duke University, where she studied the impact of immune dysregulation on the brain during various mental health conditions, including additiction and developmental disorders. She joined the faculty at the University of Delaware in 2013, where she manages three NIH grants that seek to examine the consequences of immune function on brain function across a number of mental health disorders.




Keynote talk with Q & A

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.

Delaware Neuroscience Symposium 2021

Do you have any other suggestions or comments?

Your vote has been successfully recorded.