Many of our neuroscience students apply for and conduct funded research through Pomona's Summer Undergraduate Research Program. Below are recent summer projects.

2019

Matches Made in Heaven: Receptors and Odorants in C. elegans

Priscilla Ki ’21; Advisor: Elizabeth Glater​

Caenorhabditis elegans, or commonly referred to as C. elegans, is a well-studied, bacteria-eating nematode.  Although C. elegans olfaction is well studied, most receptors have not been matched to specific ligands, an important step towards understanding how odor signals are coded in the nervous system. One olfactory neuron has multiple receptors and can tell multiple ligands apart; however, because many ligands have not yet been matched to their exact receptor, it is still unknown as to how the receptor relays that the ligand is bound, which influences chemotaxis behavior.  To find ligand and receptor matches, multiple mutant strains were tested through chemotaxis assays using known attractive odorants. Assays with one mutant strain showed that this strain is defective in detecting attractive odorants associated with the AWC olfactory neurons. This finding may indicate that gene encodes for a receptor expressed in the AWC neurons.

Characterization of Human Ganglionic Eminence Cell Behavior Upon Xenotransplantation

Eric Garcia ’21; Advisor: Elizabeth Glater​

The neocortex consists of excitatory and inhibitory neurons (IN) which maintain the balance of excitation and inhibition. Disruptions in IN development can lead to abnormal brain activity, resulting in cognitive dysfunctions and seizures. However, little is known regarding normal human IN development in the human cortex. INs are born in the ganglionic eminence (GE), a transient structure in the embryonic brain. These cells migrate to their target region in the cortex, where they differentiate into mature INs. The GE is subdivided into distinct regions: the medial, caudal, and lateral GE (MGE, CGE, and LGE). Previous xenotransplantation of human MGE (hMGE) cells to the rodent brain has shown that these cells maintain their developmental trajectory and can become functional INs . Given that the human CGE (hCGE) is also a significant contributor to the human IN population, we aim to characterize the cellular organization, proliferation, and migration of hCGE cells. In this study, hCGE cells were transplanted into the cortex of immunodeficient, neonatal mice and analyzed at 1 month post-transplant. These hCGE cells retained the ability to proliferate and migrate, yet formed a CGE-unique cellular organization distinct from the hMGE, suggesting developmental differences between GE subregions. Our results support xenotransplants as a model for human IN development, having implications for treating neurodevelopmental diseases such as epilepsy, autism and schizophrenia.

Run Faster, Run Smarter: The Relationships Between Physical Activity, Hippocampal Volume And Memory

Nathania Hartojo ’20

Studies have shown that mice who are engaged in physical activity score higher on hippocampal-dependent memory tasks. In human studies, this connection has also been found; sedentary lifestyles in children are implicated with low academic ability and decreased cognitive performance. By employing structural magnetic resonance imaging (sMRI), cognitive testing, and accelerometers to measure levels of physical activity, this study aims to discern relationships between: (1) time spent engaged in moderate-to-vigorous physical activity (MVPA) and hippocampal volume; (2), MVPA and cognitive function; and (3), hippocampal volume and cognitive function in children between the ages of 7-11. We hypothesized that children engaged in MVPA would show increased hippocampal volume, and that increased hippocampal volume would relate to higher scores in measures of hippocampal learning and memory. Linear regression analyses were used to analyze MVPA, cognitive test scores, and hippocampal volume. Outcomes were adjusted for age, sex, and BMI z-score, along with intracranial volume in volumetric analyses. Our findings indicate a positive trend between MVPA and attention (p = 0.06), but only in female participants; MVPA had no relationship to cognitive performance in male participants. In addition, we found no relationship between time spent in MVPA and hippocampal volume, though we found a strong correlation between hippocampal volume and performance on episodic memory tasks (p < 0.05).

Does An Enriched Environment Improve Learning In C. Elegans?

Marilyn Santacruz ’21; Advisor: Elizabeth Glater​

C. elegans, are roundworms used as model organisms because of their small, well-studied nervous system and fully-sequenced genome. The goal of the experiment was to examine factors that enhance learning. Specifically, we examined how being raised in an enriched environment affects learning in C. elegans. The major food source of C. elegans is bacteria. In laboratory experiments, C. elegans are most often cultivated on lawns of E. coli bacteria, but this environment is not representative of their natural environment, where C. elegans likely are exposed to multiple bacterial species. To mimic this more natural environment, we raised worms on plates with several bacteria. We then compared the learning behavior of these worms to worms raised on E. coli only. To examine their learning, we used an associative learning assay. The assay consists of starving them in a petri dish, with an attractive odorant added to the lid. In chemotaxis assays, we expect to see a repulsion to this odorant because the worms have learned to associate the odorant with starvation. If an enriched environment enhances learning, we expect to see worms raised with multiple bacteria to be more repulsed by isoamyl alcohol than worms raised on a single bacterium. In these experiments, C. elegans grown in an enriched environment showed moderately enhanced learning and C. elegans grown in just Pseudomonas sp., showed increased learning from those grown in just E. coli and in an enriched environment.

The Identification and Characterization of the First CSPG in Drosophila Melanogaster

Sammy Little ’20; Advisor: Karl Johnson

Chondroitin sulfate proteoglycans (CSPG’s), extracellular matrix molecules recognized for their roles in vertebrate nervous system development, have yet to be identified in Drosophila melanogaster. We identified the first CSPG in Drosophila using Western blot staining against Windpipe, formerly a candidate CSPG. We also utilized CRISPR/Cas9 mutagenesis to knock out 4-O Sulfotransferase (4-OST) to complete the stepwise knockout of enzymes in the biosynthetic pathway of CSPGs. Finally, we aimed to identify the localized functions of CSPGs in Drosophila by creating rescue constructs of the previously knocked out biosynthetic enzymes Chondroitin Synthase (ChSy) and Chondroitin Polymerizing Factor (CPF).

Effects Of Dithiocarbamate Pesticide Ziram On Voltage-Gated Potassium Channels In Idiopathic Parkinson's Disease

James Kelbert ’20; In partnership with the 5C Neuroscience Fellowship

Environmental toxins, such as the dithiocarbamate fungicide ziram, have been to used as an entry point to uncover potential pathways involved in Parkinson’s disease. To uncover the mechanisms that connect ziram to PD, we examined the effects of acute ziram exposure on neurotransmission. Previous work from the Schweizer lab demonstrates that ziram dose-dependently increases glutamatergic and aminergic excitability at the Drosophila neuromuscular junction (NMJ). Using a mutant screen, we have shown that hypomorphic mutants of the ether-a-go-go (eag) potassium channel phenocopies ziram-induced excitability and occludes further ziram action. We are now testing whether mammalian orthologues of eag are targets of ziram. We initially focus on 3 of the eight KCNH family members: human ether-a-go-go related gene (hERG, Kv 11.1), ether-a-go-go like potassium channel (ELK, Kv12.1), and human ether-a-go-go gene (hEAG, Kv 10.1). hERG is of special interest, since it encodes a delayed rectifier potassium channel (Kdr), which plays a pivotal role in both neural and cardiac repolarization. Utilizing the HEK 293T cell line and voltage clamp electrophysiology, we provide preliminary results that suggest acute ziram exposure disrupts hERG potassium currents (n=4). Acute ziram exposure did not affect EAG potassium currents (n=5) while it did potentiate ELK potassium currents (n=3); due to small sample size, more experiments must be done to further confirm the effects of acute ziram exposure.

Modeling the Distribution of Synaptic Ribbons in the Chinchilla Utricle and Crista Ampullaris

Eva Gontrum ‘20; Advisor: Tom Borowski​

Vestibular afferent signals from the semicircular canal and otolith organs are necessary for the stabilization of gaze, all cognitive aspects of balance and self-orientation, as well as movement and spatial navigation. This offers an explanation for why the vestibular system is one of three sensory transduction systems that functions with the synaptic ribbon, an electron-dense ball or disc tethered to small clear vesicles, continuously modulated by subtemporal precision. Specialized for a rapid tonic neurotransmitter release, synaptic ribbons provide a readily-releasable and continuous pool of vesicles, essential for input that is specialized to transmit analog signals, such as intensity. Studies in the chinchilla provide a model for a highly active mouse, as the chinchilla engages in a “whisking” behavior that is not an identifying characteristic in mouse. Increased head kinematics in a species is expected to increase the number of ribbon synapses in the vestibular system, as a more highly specialized signal transduction network with a greater potential for high-volume excitatory transmission is necessary for animals with superior behavioral agility. The heterogeneity of synaptic ribbons, afferents, and efferents, offers an impressive array of coding mechanisms for a variation in vestibular function. I report heterogeneity in number and size of synaptic ribbon (modeled using diameter of synaptic ribbon) as a measurement for sensory adaptions specific to the chinchilla.

Chondroitin Synthase (Chsy) Mutants Show Decreased Synaptic Size Compared To Wild Type And Galnact Mutants

Isabella Izquierdo ’20; Advisor: Karl Johnson

Chondroitin Sulfate Proteoglycans (CSPGs) are molecules found in the extracellular matrix (ECM) that play a crucial role in guiding axonal growth during neurodevelopment as well as for spinal cord regeneration. CSPGs are proteoglycans made up from a core protein and chondroitin sulfate sugar side chains. This study aims to identify the first CSPGs in Drosophila and to examine the role of these proteoglycans during Drosophila central nervous system development. Chondroitin Synthase (ChSy) mutants lack the majority of their chondroitin sulfate sugar side chains and exhibit extremely reduced movement speed during larval stages in comparison to wild type. Most of these flies remain stuck in their pupal cases when attempting to hatch. To examine the neuromuscular junction of these mutants, we stained the synapses of several different strains of mutant Drosophila including ChSy and GalNAcT mutants using antibodies against synaptic proteins such as HRP, NC82, 6D6, and Fas(II). We imaged these synapses using a confocal microscope. Due to the impaired motility of these mutants, we hypothesize that synaptic development of the ChSy mutants will differ from that of the GalNAcT mutants and wild type during the third instar larval stage.

The Head & Foot Connection: Small Head Turn, Turnside Foot Weighs more!

Hannah Dorris ’20; Advisor: Richard Lewis

The objective of this research is to gain fundamental knowledge about the role of head turning on shifting weight to the turnside foot. Subjects will perform a series of head turns, varying the angle of the head turn at 10 beats per minute, and the normal force under their feet will be measured. The percent turnside force, calculated by the turnside force over turnside force plus opposite side force, will provide vital information about the amount of weight shifted to foot underneath the side of the head turn (i.e. from the movement of the head, does weight shift to the side of the turnside force? How does this weight shift vary based on the angle of the head turn?). We hypothesize that individuals will shift 25% of their weight to the turnside foot. Additionally, this weight that is shifted will be “dose dependent,” whereas the smaller angles (45 degrees) will show less of a turnside weight shift than the larger (60 degree, 90 degree) angles. During a head turn (45, 60, or 90 degrees), the turnside foot's normal force increased by .7-1% on average, and the FFT magnitude was higher for the "turning trials," displaying a rhythmic pattern of foot force-shifting to the 10 bpm. Although we hypothesized there would be a dose dependent effect based off the degrees someone is turning, we saw a consistent change of .7-1%, not dependent on the degree turn.

Perception and Behavioral Response of Caenorhabditis elegans to Odor Blends

Micah Maglasang ’20; Advisor: Elizbeth Glater​

The nematode Caenorhabditis elegans provide a simple model to study how sensory stimuli are received, encoded, and perceived by the nervous system.  C. elegans uses chemosensation to locate food, avoid potentially harmful substances, and reproduce (Bargmann 2006). However, how C. elegans recognizes mixtures of odorants to detect bacteria, its major food source, is not yet fully understood. In this study, we elucidate how C. elegans recognizes an odor bouquet consisting of multiple odorants. We will conduct an associative conditioning assay in which C. elegans are starved in the presence of a specific odorant or odor blend, called the conditioning odor.  After the starvation period, we will conduct chemotaxis assays to observe the chemotactic response of conditioned and naive worms to the conditioning odor. We expect that conditioned worms will have a reduced attraction to the conditioning odor blend, but not other odor mixtures, because the worms have learned to associate starvation with the specific odor mixture.  Results have shown that conditioned worms display a reduced attraction to both the conditioning odor as well as blends containing various concentrations of the conditioning odor. We plan to conduct further associative conditioning assays as well as calcium imaging to study the activity of sensory neurons in response to odors in conditioned and well-fed worms. We hope to gain a better understanding of mechanisms underlying sensory processing and perception.

Recruitment Of Lysosomes To Phagocytic Cups Is Translation-Dependent In Microglia

Sophie Bax ’20; Advisor: Elizabeth Glater​

Microglia, the tissue-resident immune cells of the brain, play a critical role in neurodevelopment, the clearance of cellular debris from the brain parenchyma, the brain’s response to infection, and the etiology of certain neurodegenerative diseases. Highly motile cells, they are constantly engaged in a survey of the surrounding brain tissue, making frequent contacts with nearby synapses. When faced with a dead cell or inactive synapse, the distal processes of the microglia engulf the debris via phagocytosis. Previous work by Vasek et al. (unpublished) using microglial translating ribosomal affinity purification (TRAP) coupled to RNA-seq revealed a distinct local translatome in the distal processes of microglia, in which genes responsible for phagocytosis and cell motility are enriched. This study aimed to corroborate these findings by visualizing translation in the distal processes using ex vivo puromycilation assays and immunostaining in mouse forebrain slices. Using the myeloid cell-specific lysosomal marker CD68, I show that lysosomes localize to phagocytic cups in microglia. Pretreatment with anisomycin, a translation-inhibiting antibiotic, minimizes CD68 signal at phagocytic cups, suggesting that translation is required for the recruitment of lysosomes to the phagocytic cups.

Chondroitin Synthase (ChSy) Mutants Show Decreased Synaptic Size Compared to Wild Type and GalNacT Mutants

Annika Kim ’20; Advisor: Karl Johnson

Chondroitin Sulfate Proteoglycans (CSPGs) are molecules found in the extracellular matrix (ECM) that play a crucial role in guiding axonal growth during neurodevelopment as well as for spinal cord regeneration. CSPGs are proteoglycans made up from a core protein and chondroitin sulfate sugar side chains. This study aims to identify the first CSPGs in Drosophila and to examine the role of these proteoglycans during Drosophila central nervous system development. Chondroitin Synthase (ChSy) mutants lack the majority of their chondroitin sulfate sugar side chains and exhibit extremely reduced movement speed during larval stages in comparison to wild type. Most of these flies remain stuck in their pupal cases when attempting to hatch. To examine the neuromuscular junction of these mutants, we stained the synapses of several different strains of mutant Drosophila including ChSy and GalNAcT mutants using antibodies against synaptic proteins such as HRP, NC82, 6D6, and Fas(II). We imaged these synapses using a confocal microscope. Due to the impaired motility of these mutants, we hypothesize that synaptic development of the ChSy mutants will differ from that of the GalNAcT mutants and wild type during the third instar larval stage.

2-Arachadinoylglycerol Signaling Mediates The Specificity Of Fear Memories

Edmund Havener ’21; Advisor: Jonathan Moore

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops following exposure to a traumatic event. In PTSD, patients may experience an over-generalization of their fear responses to normally safe stimuli. Understanding the mechanisms for pathological fear generation and anxiety may lead to development of better treatments for PTSD. The endocannabinoid (eCB) system is a retrograde neurotransmitter system that has been implicated in regulating fear and anxiety. Particularly, 2- arachidonoylglycerol (2-AG), one of the major centrally active eCB lipids, is thought to mediate resiliency to traumatic experiences. To explore the role of 2-AG in mediating fear response, we conditioned mice to fear a specific context, context A, by administering aversive shocks. We repeated this procedure until the mice were observed to freeze at least 60 percent of the time in context A. Freezing is a species-specific response to fear, and is often used as a proxy for fear in rodents. Finally, we placed half the mice in context A again, and the other half in a novel context, context B. Before placing the mice in their respective context, we blocked 2-AG synthesis in half of each group of mice. Blocking 2-AG synthesis increased the level of freezing of the mice in the novel context. This leads us to believe that 2-AG deficient states may increase the likelihood of developing pathological fear generalization following a traumatic experience.

The Effects of Other vs. Self, Social vs. Non-Social and Collectivist-Individualist Orientation on BA10 Activation

Soham Khan ’21; Advisor: Richard Lewis

Prospective memory (PM) refers to the ability to remember to execute an intention in the future (Dong, Wong, & Luo, 2018). Cultural factors such as individualism and collectivism largely shape and motivate social behaviors (Markus & Kitayama, 2010). Cultural differences can result in unique patterns of cognitive processing, including the encoding and retrieval of memories (Huff, Ligouri, & Gutchess, 2015). Slide-based, PM task performance has been associated with activation of the anterior prefrontal cortex (BA10) (e.g., Dong, Wong, & Luo, 2018).

We hypothesized the main effects that social-oriented and collectivist interactions would evoke greater BA10 activation than individually-oriented and individualist ones, respectively. We also explored the association between other- and self-oriented interactions within the context of the study. Since cultural differences in articulating self-identity may influence how participants respond to social and non-social cues, we additionally hypothesized a series of two-way interactions, such that collectivists would exhibit greater activation of BA10 in social- and other-oriented conditions relative to their individualist peers.

31 (18 female; 13 male) undergraduate students participated in the study. Participants were asked to memorize a total of 24 PM items comprising of various types of interaction (social, nonsocial) and intention (self, other). The stimuli presentations were randomly interspersed with distractor items.

2017

Syndecan23 Mutation in Drosophila melanogaster Affects Odor Response as well as Learning and Memory Capabilities

Dena Arizanovska ’18; Advisor: Karl Johnson; Collaborator: Jonathan King ’18

Syndecan (Sdc) is a transmembrane heparan sulfate proteoglycan that plays a role in axon guidance during development in Drosophila melanogaster. To better understand the effect of syndecan on behavior, we used Sdc23 mutant D. melanogaster larvae to examine odor preference and the capacity for learning and memory. To do this, we performed a series of olfaction assays in both wild type and mutant larvae to characterize naive odor response before adding a training period to identify the ability for associative learning. Our results showed that Sdc23 larvae prefer odors that wild type larvae do not respond to, suggesting a difference in odor receptor pathways and wiring. In addition, associative learning has been documented in wild type larvae, yet we did not find evidence of associative learning in Sdc23 larvae, which suggests that the syndecan mutation interferes with learning and memory capacity in D. melanogaster larvae.
Funding Provided By: The Elgin Fund for Summer Student Research and The Summer Undergraduate Research Program (SURP)

GREAT Knee Pain Reduction Trial

Cassandra Palmer ’18; Advisor: Matthew Sazinsky

Total knee arthroplasty (TKA) surgeries are becoming increasingly popular as general population lives longer. TKAs are great options for patients that suffer from severe osteoarthritis, however, with this procedure often comes postoperative pain that can last as long as 3-4 years. Acute postoperative pain puts patients at higher risk of developing chronic pain. Resulting from postoperative pain and other issues, there is a dissatisfaction that many patients feel after TKA surgeries. Genicular nerve radiofrequency ablation (RFA) is a procedure commonly performed in chronic knee osteoarthritic nonsurgical patients and has been found to vastly improve pain symptoms. The aim of this prospective, randomized, double-blinded clinical trial is to determine the efficacy of genicular nerve RFA in improving acute and chronic postoperative pain. TKA patients that fit the criteria will be randomly assigned either a treatment group receiving the RFA procedure or a control group without treatment (placebo). Exactly 60 patients (30 in each group) will be followed preoperatively and postoperatively with a series of surveys and tests including an 11-point Pain Intensity Numerical Rating Scale (PI-NRS). The main analysis will look at the difference between the experimental and control group PI-NRS mean score; significant difference has been determined to be 2 points of the mean. Unfortunately, due to funding issues, the study has not begun.
Funding Provided By: Dale N. Robertson Fund for Undergraduate Research

Identifying CSPGs in Drosophila Melanogaster

German Rojas ’18; Advisor: Karl Johnson

Chondroitin sulfate proteoglycans (CSPGs) are extracellular proteins involved in neural development and glial scar formation following CNS injury. During development, CSPGs have been shown to help guide axons; however, in spinal cord injury, CPSGs inhibit axonal regeneration. However, the mechanisms behind their actions are not yet fully understood. CSPGs have yet to be identified in Drosophila melanogaster, but there is evidence to suggest they exist, including the presence of CS in flies, and the presence of highly conserved CS biosynthetic enzymes in the fly genome. In this study, we are using syndecan, a heparan sulfate proteoglycan (HSPG) and biochemistry techniques, and we have found a potential way to identify and study the mechanisms underlying CSPG function in D. melanogaster.
Funding Provided By: Rose Hills Foundation SURP Grant

Metabolic labeling of Drosophila S2 cells with N-acetylgalactosamine and N-acetylglucosamine

Lauren Callans ’18; Advisor: Karl Johnson

Chondroitin sulfate proteoglycans (CSPGs) have been previously implicated in both neural development and spinal cord injury as repulsive growth molecules. CSPGs have not yet been identified in Drosophila melanogaster despite containing the highly-conserved sequences for necessary biosynthetic enzymes. Furthermore, the conservation of chondroitin and its function in related organisms, such as Caenorhabditis elegans, and the evidence suggesting the addition of chondroitin sulfate in syndecan over-expressing cells strongly suggest that Drosophila produce CSPGs. In this study, metabolic labeling was used to incorporate azide-tagged N-acetylgalactosamine or N-acetylglucosamine, sugars necessary for glycosylation of CSPGs and heparan sulfate proteoglycans (HSPGs) respectively, into Drosophila S2 cell proteins. Cells were incubated with the azide-tagged sugars for 48 hours to allow for incorporation. After incubation, a Click Chemistry reaction involving biotin alkyne was used to selectively draw CSPGs out of solution. Further optimization of the incorporation and reaction protocols is necessary before definitive conclusions can be made regarding the utility of metabolic labeling to identify CSPGs in Drosophila.
Funding Provided By: Fletcher Jones Foundation

The Effect of Reading Intervention on the Structure of the Dyslexic Brain

Mark Penrod ’18; Advisor: Nicole Weekes

Reading and language processing are two of the most fundamental cognitive tasks our brains carry out. However, certain reading disabilities, such as dyslexia, interfere with the brain’s ability to perform those tasks. Despite the growing number of cases of reading disability, there is not much consensus on the neural correlates of the disease or its effect on the development of the brain. In order to tackle these concerns, we studied a group of reading disabled children from ages 8-12 as they underwent 160 hours of intensive reading training. Before, during, and after the intervention, information on the structure of the brain was collected via magnetic resonance imaging (MRI). Children in the program unanimously improved significantly in various reading measures throughout the intervention. Additionally, a concurrent study suggests that changes in white matter between areas known to be involved in reading occur simultaneously. In this study, changes in cortical thickness were tracked and analyzed across the cerebral cortex throughout the intervention program. Preliminary results suggest a correlation between reading ability and cortical thickness in primary auditory and visual processing areas, as well as areas (such as the fusiform gyrus) known to be associated with the integration of phonological and visual information. Furthermore, longitudinal analysis indicates that cortical thickness decreases in these areas as reading-disabled children undergo intervention.
Funding Provided By: General SURP Fund

How do you see me? How age, emotion, and individual differences influence face processing and the N170.

Morgan Berlin ’19; Advisor: Jonathan King

With aging, our ability to process information changes: some processing improves with increased expertise while other processing, which relies on speed and working memory, may worsen. We investigated how aging affects the neural processing of human faces by comparing the N170 event-related potential across younger and older age groups. One experiment examines how age, anxiety, depression, and cognitive processing speed influence the amplitude and latency of the N170 when categorizing visual stimuli as faces or cars. The second experiment examines the interaction of facial emotional expressing and the "own-age" effect on the N170 component. The "own age" effect refers to our ability to preferentially process faces of people our own age (i.e., younger people recognize other younger people better than older people). We use a 1-back paradigm in which participants determine whether a face is the same face as shown in the previous trial or if an emotional expression is the same expression as shown in the previous trial. Participants then complete a memory task and social experience questionnaires. We predict that the interaction of age and emotion on the amplitude of the N170 will be mediated by social experience and cognitive processing abilities. Comparing the results from these two experiments will tell us how different processes involved in face processing may be maintained and changed with aging.
Funding Provided By: Paul K. Richter and Evalyn E. Cook Richter Memorial Fund

CRISPR/Cas9 Knockout of Biosynthetic Enzymes for CSPGs

Eric Smith ’19; Advisor: Karl Johnson

Chondroitin sulfate proteoglycans (CSPGs) are extracellular matrix molecules known for their role in nervous system development in vertebrates. Although they have been identified in humans and other species, CSPGs have yet to be identified in Drosophila melanogaster. Close relatives to CSPGs, heparan sulfate proteoglycans (HSPGs), have been shown in Drosophila to be key regulators of central nervous system development. The aim of this study is to explore whether CSPGs are present in Drosophila by knocking out the candidate CSPG biosynthetic enzymes using the CRISPR/Cas9 mutagenesis method.
Funding Provided By: Evelyn B. Craddock McVicar Memorial Fund

Disentangling apathy subtypes in Huntington’s Disease: a white matter biomarker of disease profile and progression

Audrey DePaepe ’18; Advisor: Ruth Diego-Balaguer

Along with motor and cognitive deterioration, neuropsychiatric symptoms form a common feature of Huntington’s disease (HD). Of these, apathy has been shown to highly correlate with disease progression, often emerging prior to clinical diagnosis. However, due to the multidimensional nature of apathy, its elusive etiology, and the lack of operative diagnostic criteria, treatment options are limited. In the present study, the global apathy measures of the short-form Lille Apathy Rating Scale (LARS) and the short Problem Behavior Assessment (PBA-s) correlated when assessed in pre-manifest and Stage I patients. Both apathy measures also correlated with Total Functional Capacity (TFC), a measure of disease severity. In addition, factor analysis of the LARS generated a dimensionalization of measured apathy into its three subtypes: emotional, cognitive, and auto-activation deficit. Further analysis by diffusion tensor imaging (DTI) revealed a significant relationship between global apathy and diffusion measures corresponding to a bilateral decrease in white matter (WM) integrity of the frontostriatal tract (FST). Moreover, higher levels of subtype-specific apathy correlated with a right-lateralized decrease in structural connectivity in the FST for the cognitive domain and in the uncinate (UC) for the emotional domain of apathy. That apathy subtypes are associated with distinct WM substrates supports the importance of an individualized approach to its diagnosis and treatment.
Funding Provided By: N/A