Neuroscience and Neurobiology Commons^™

Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich

Dissertations, Theses, and Capstone Projects

Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of …

Effects Of Mindfulness Meditation On Selective, Sustained Attention, Brain Neural Oscillations, And Short-Term Memory, Anamaria Guzman

Honors Program: Senior Projects (Public)

The following extended literature review and research proposal study started initially as a complete research proposal but, due to the challenges COVID-19 has brought, it has become a stand-alone piece of work without data collection. The goal is to synthesize a broad range of literature and previous research on mindfulness meditation and its effects on attention, memory, and brain activity and thus, offering a new perspective and a proposed research path on this subject. This proposed research study, besides previous studies, indicates that mindfulness meditation is expected to improve and enhance selective and sustained attention, which results in better attentional …

Changes In The Gut Microbiome Following Traumatic Stress Exposure In A Mouse Model Of Post-Traumatic Stress Disorder (Ptsd), Rebecca Schultz, Veronica Piggott, Alana C. Conti

Medical Student Research Symposium

Posttraumatic stress disorder (PTSD) can occur following exposure to extreme adverse events, affecting 6.8% of adult Americans. There is a positive correlation between PTSD and gastrointestinal (GI) pain and upset, with the origin of these GI issues attributed to bacterial changes in the gut microbiome. Animal studies have shown a relationship between stress and GI dysfunction, leading to increased systemic lipopolysaccharide (LPS) levels, which have been linked to neuroinflammation and cognitive impairment. The bidirectional and complex communication between microbiota and the brain is not fully understood and therefore would benefit from further experimental studies. Therefore, the goal of my project …

Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun

Neuroscience Faculty Publications

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix.

For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020).

Survey Of Prevention And Intervention Strategies Reducing Return To Play Post-Concussion In Division 1 Football, Joseph F. Clark, Enna Selmanovic, Kip Drewry, Jon Vincent, Aaron Himmler, Bob Mangine, Kim Hasselfeld, Jane Khoury, David Polanski, Jon Divine

Journal for Sports Neuroscience

Abstract.

Introduction

Sports related concussion, also considered mTBI, has remained in the public eye due to heightened fear concerning playing football and other collision based sports. Concussion prevention, as well as rehabilitating the brain after a concussion, is a high priority for many sports medical practitioners as well as for athletes. For these reasons, researchers associated with the American Athletic Conference (AAC) have surveyed concussion incidence in football. One of the AAC teams engaged in regular neurovisual training (NVT) and concluded this training program is associated with faster return to play post-injury in this observational cohort study.

Methods

The …

An Objective Method To Assess And Recommend Exertion And Exercise Targets For Return To Play Post Concussion, Joseph F. Clark Phd Atc, Robert E. Mangine Pt Med Atc, Kimberly A. Hasselfeld Ms, Violet T. Schramm, Angelo J. Colosimo Md, Aaron Kuehn-Himmler At Ms, Gerald M. Holloway Ms Atc, Faniel Fosselman Do Mba, Jon Vincent, Nicole Giordano, Jon G. Divine Md Ms

Journal for Sports Neuroscience

Introduction.

Concussions are of significant concern for athletic trainers, and there is a critical need to objectively and safely allow an athlete to return to play. In sports the objective is return as safely and soon as possible. Exertion is a consideration regarding progressing an athlete back to play. The ability to exert in cardiovascular and strength and conditioning contexts are two critical steps in most return to play protocols. Being able to make objective recommendations is urgently needed, as trial and error leads to unnecessary risk of eliciting symptoms and/or causing setbacks.

Objective.

The object of this paper is …

Next-Generation Diamond Electrodes For Neurochemical Sensing: Challenges And Opportunities, Erin K. Purcell, Michael F. Becker, Yue Guo, Seth A. Hara, Kip A. Ludwig, Collin J. Mckinney, Elizabeth M. Monroe, Robert Rechenberg, Cory A. Rusinek, Akash Saxena, James R. Siegenthaler, Caryl E. Sortwell, Cort H. Thompson, James K. Trevathan, Suzanne Witt, Wen Li

Chemistry and Biochemistry Faculty Research

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good …

Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation, April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines

Psychology Faculty Research

© 2021, The Author(s). Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we …

A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson

Department of Paediatrics and Child Health

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.
Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts. …

Prediction Of Alzheimer’S Disease-Specific Phospholipase C Gamma-1 Snv By Deep Learning-Based Approach For High-Throughput Screening, Sung Hyun Kim, Sumin Yang, Key Hwan Lim, Euiseng Ko, Hyun Jun Jang, Mingon Kang, Pann Ghill Suh, Jae Yeol Joo

Computer Science Faculty Research

© 2021 National Academy of Sciences. All rights reserved. Exon splicing triggered by unpredicted genetic mutation can cause translational variations in neurodegenerative disorders. In this study, we discover Alzheimer’s disease (AD)-specific single-nucleotide variants (SNVs) and abnormal exon splicing of phospholipase c gamma-1 (PLCγ1) gene, using genome-wide association study (GWAS) and a deep learning-based exon splicing prediction tool. GWAS revealed that the identified single-nucleotide variations were mainly distributed in the H3K27ac-enriched region of PLCγ1 gene body during brain development in an AD mouse model. A deep learning analysis, trained with human genome sequences, predicted 14 splicing sites in human PLCγ1 gene, …

Nmda Receptors Enhance The Fidelity Of Synaptic Integration, Chenguang Li, Allan Gulledge

Dartmouth Scholarship

Excitatory synaptic transmission in many neurons is mediated by two coexpressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in kinetics, ion selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here, we report that the voltage dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of EPSPs across spatial and volt- age domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees re- vealed that the combined presence of AMPA and NMDA conductances reduce the variability of …

Practical Recommendations For Timely, Accurate Diagnosis Of Symptomatic Alzheimer’S Disease (Mci And Dementia) In Primary Care: A Review And Synthesis, J. L. Liss, S. Seleri Assunção, Jeffrey Cummings, A. Atri, D. S. Geldmacher, S. F. Candela, D. P. Devanand, H. M. Fillit, J. Susman, J. Mintzer, T. Bittner, S. A. Brunton, D. R. Kerwin, W. C. Jackson, G. W. Small, G. T. Grossberg, C. K. Clevenger, V. Cotter, R. Stefanacci, A. Wise-Brown, M. N. Sabbagh

School of Medicine Faculty Research

The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early …

Neural Dynamics, Adaptive Computations, And Sensory Invariance In An Olfactory System, Srinath Nizampatnam

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sensory stimuli evoke spiking activities that are patterned across neurons and time in the early processing stages of olfactory systems. What features of these spatiotemporal neural response patterns encode stimulus-specific information (i.e. ‘neural code’), and how they are translated to generate behavioral output are fundamental questions in systems neuroscience. The objective of this dissertation is to examine this issue in the locust olfactory system. In the locust antennal lobe (analogous to the vertebrate olfactory bulb), a neural circuit directly downstream to the olfactory sensory neurons, even simple stimuli evoke neural responses that are complex and dynamic. We found each odorant …

Constructing And Analyzing Neural Network Dynamics For Information Objectives And Working Memory, Elham Ghazizadeh Ahsaei

McKelvey School of Engineering Graduate Student Theses & Dissertations

Creation of quantitative models of neural functions and discovery of underlying principles of how neural circuits learn and compute are long-standing challenges in the field of neuroscience. In this work, we blend ideas from computational neuroscience, information and control theories with machine learning to shed light on how certain key functions are encoded through the dynamics of neural circuits. In this regard, we pursue the ‘top-down’ modeling approach of engineering neuroscience to relate brain functions to basic generative dynamical mechanisms. Our approach encapsulates two distinct paradigms in which ‘function’ is understood. In the first part of this research, we explore …

Neural Coding And Organization Principles In The Drosophila Olfactory System, Haoyang Rong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sensory systems receive and process external stimuli to allow an organism to perceive and react to the environment. How is sensory information subsequently represented, transformed, and interpreted in the neural system? In this dissertation, I have investigated this fundamental question using the fruit fly (Drosophila melanogaster) olfactory system.Chemical cues are transduced into neural signals in the insect antenna by the olfactory receptor neurons (ORNs). The ORNs send their axons to the antennal lobe (AL), with each ORN type innervating a specific neuropil (glomerulus), where they synapse onto excitatory and inhibitory projection neurons (ePNs and iPNs). The ePNs project their axons …

Oligodendroglial Epigenetics, From Lineage Specification To Activity-Dependent Myelination, Mathilde Mathilde Pruvost, Sarah Moyon

Advanced Science Research Center

Oligodendroglial cells are the myelinating cells of the central nervous system. While myelination is crucial to axonal activity and conduction, oligodendrocyte progenitor cells and oligodendrocytes have also been shown to be essential for neuronal support and metabolism. Thus, a tight regulation of oligodendroglial cell specification, proliferation, and myelination is required for correct neuronal connectivity and function. Here, we review the role of epigenetic modifications in oligodendroglial lineage cells. First, we briefly describe the epigenetic modalities of gene regulation, which are known to have a role in oligodendroglial cells. We then address how epigenetic enzymes and/or marks have been associated with …

Alzgps: A Genome-Wide Positioning Systems Platform To Catalyze Multi-Omics For Alzheimer’S Drug Discovery, Yadi Zhou, Jiansong Fang, Lynn M. Bekris, Yeon Heon Kim, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng

School of Medicine Faculty Research

Background: Recent DNA/RNA sequencing and other multi-omics technologies have advanced the understanding of the biology and pathophysiology of AD, yet there is still a lack of disease-modifying treatments for AD. A new approach to integration of the genome, transcriptome, proteome, and human interactome in the drug discovery and development process is essential for this endeavor. Methods: In this study, we developed AlzGPS (Genome-wide Positioning Systems platform for Alzheimer’s Drug Discovery, https://alzgps.lerner.ccf.org), a comprehensive systems biology tool to enable searching, visualizing, and analyzing multi-omics, various types of heterogeneous biological networks, and clinical databases for target identification and development of effective prevention …

Resting Cerebral Oxygen Metabolism Exhibits Archetypal Network Features, Nicholas A. Hubbard, Monroe P. Turner, Kevin R. Sitek, Kathryn L. West, Jakub R. Kaczmarzyk, Lyndahl Himes, Binu P. Thomas, Hanzhang Lu, Bart Rypma

Center for Brain, Biology, and Behavior: Faculty Publications

Standard magnetic resonance imaging approaches offer high-resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low-frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual-echo, pseudocontinuous arterial spin labeling, and blood-oxygen-level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic …

Recallable But Not Recognizable: The Influence Of Semantic Priming In Recall Paradigms, Jason D. Ozubko, Lindsey Ann Sirianni, Fahad N. Ahmad, Colin M. Macleod, Richard Addante

Psychology Faculty Publications

When people can successfully recall a studied word, they should be able to recognize it as having been studied. In cued-recall paradigms, however, participants sometimes correctly recall words in the presence of strong semantic cues but then fail to recognize those words as actually having been studied. Although the conditions necessary to produce this unusual effect are known, the underlying neural correlates have not been investigated. Across five experiments, involving both behavioral and electrophysiological methods (EEG), we investigated the cognitive and neural processes that underlie recognition failures. Experiments 1 and 2 showed behaviorally that assuming that recalled items can be …

Neural Correlates Of The Dunning-Kruger Effect, Alana Muller, Lindsey A. Sirianni, Richard Addante

Psychology Faculty Publications

The Dunning-Kruger effect (DKE) is a metacognitive phenomenon of illusory superiority in which individuals who perform poorly on a task believe they performed better than others, yet individuals who performed very well believe they under-performed compared to others. This phenomenon has yet to be directly explored in episodic memory, nor explored for physiological correlates or reaction times. We designed a novel method to elicit the DKE via a test of item recognition while electroencephalography (EEG) was recorded. Throughout the task, participants were asked to estimate the percentile in which they performed compared to others. Results revealed participants in the bottom …

From Crib To Bench: Understanding Neonatal Opioid Withdrawal Syndrome (Nows) Using A Novel Rodent Model, Sarah Stevens

Theses, Dissertations and Capstones

As the opioid epidemic continues to grow, opioid use among pregnant women is increasing significantly. This has led to a steady rise in the number of infants born with neonatal opioid withdrawal syndrome (NOWS). Although short-term withdrawal symptoms associated with NOWS are well characterized, there are many gaps in our understanding of the short and long-term effects of prenatal opioid exposure. In CHAPTER 1, we describe the clinical presentation, associated neurodevelopmental challenges, and current treatments of NOWS. Our current understanding of the neuropathology of NOWS is limited, and therefore further research is needed. However, current animal models are limited by …

Extracellular Vesicles From Uvb Irradiated Keratinocytes Contain Cyclobutane Pyrimidine Dimers, Meghana Reddy Ginugu

Browse all Theses and Dissertations

Ultraviolet (UV) radiation induces the formation of cyclobutane pyrimidine dimers (CPDs) in genomic DNA, which are normally removed by nucleotide excision repair. However, the fate of these adducts remain largely unexplored. Detection of these photoproducts in body fluids could act as a predictor of UV exposure and enable a better understanding of the pathogenesis of photosensitive skin diseases, such as lupus. Using cultured human keratinocytes exposed to UVB radiation in vitro, ultracentrifugation of cell culture supernatants, and immunodot blot analysis of isolated DNA, we have found that a small fraction of CPDs is released from cells in a dose- and …

Neuroglobin And Its Role In The Recovery Of Neuronal Cells In Hypoxic Conditions Using Hypoxia Inducible Factor– 1, Riya Shah

Honors Undergraduate Theses

Stroke is the world's leading cause of adult disability, caused by lack of oxygen and nutrients to the brain due to a blood clot in a major artery. This leads to ischemic damage of neuronal cells that leads to paralysis, motor, and speech deficits. While most stroke therapies aim at removing or reducing the blood clots in the brain, few treatments target cell damage. Neuroglobin (NGB) is a protein in the brain that is able to aid in neuroprotection following oxidative stress. Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor that serves as a marker for cell recovery after hypoxia or …

Diversifying Participation: The Rarity Of Reporting Racial Demographics In Neuroimaging Research, Madeline Goldfarb

Pitzer Senior Theses

Background: Functional neuroimaging techniques have been instrumental to progress in the cognitive and behavioral sciences; however, their increasing prevalence has evoked conversations concerning limitations associated with reproducibility and bias (Gilmore et al., 2017). While the literature has explored several mechanisms driving issues of replicability, few discussions have considered the effects of confounding social and environmental variables such as age, sex, socioeconomic status, and race (Sauce & Matzel, 2013). The prevailing racial, cultural, and socioeconomic bias in scientific research and the methodological limitations of EEG perpetuate racial and ethnic homogeneity in participation, eliciting qualms regarding the generalizability of findings (Henrich et …

The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Akap95 And Cyclin D3 Expression, Kyle P. Kenney, Mary Pistack, Angela Asirvatham

Student Research Poster Presentations 2021

Schwann cells are a vital component of the Peripheral Nervous System and aid in the repair of axons following injury. The regulation of Schwann cell growth in vitro is facilitated by heregulin, a neuron-secreted growth factor, and an unknown mitogen that activates the cyclic adenosine monophosphate (cAMP) pathway. The abundance of intracellular cAMP is regulated by a family of enzymes called phosphodiesterases (PDEs). PDE inhibitors such as rolipram have therapeutic potential in various disorders and function by increasing the levels of intracellular cAMP. A-Kinase anchoring proteins (AKAPs), a family of scaffolding proteins that belong to the cAMP/Protein Kinase A (PKA) …

Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain

Theses and Dissertations

Gene expression is regulated at multiple levels, including transcription, RNA editing, pre-mRNA splicing, mRNA export, translation, and posttranslational modifications. Alternative splicing is a process by which exons can be included or excluded, giving rise to multiple mRNA isoforms from the same transcript. Alternative splicing is an important mechanism in developmental, tissue- and cell-specific control of gene expression, and it is key for expanding proteomic diversity and complexity from a limited number of genes. Moreover, more than 95% of multiexon genes undergo alternative splicing in humans, and about half of all disease-causing point mutations in humans affect pre-mRNA splicing, including neurological …

Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen

Theses and Dissertations

Parkinson’s disease (PD) is the most common movement disorder and is characterized by neuronal loss and the presence of Lewy bodies in dopaminergic neurons of the substantia nigra pars compacta. PD is a chronic, progressive, and irreversible neurodegenerative disorder associated with the selective loss of dopaminergic neurons. Initially described in an Ayurvedic medical treatise and Galen’s writings, and later by James Parkinson in 1817, the most common symptoms of PD are resting tremors, abnormal posture and gait, and muscle rigidity. Approximately 1 million people are living with PD in the United States and worldwide estimates are between 7 and 10 …

Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi

Theses and Dissertations

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder predominately affecting the aging population. It is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) affecting over 1 million individuals in the US alone. Recent studies have tried to understand the exact nature in which healthy neurons transition to a degenerative state in PD. There are a multitude of combinatory factors that can lead to the development of PD including environmental factors, genetic factors, and aging. The majority of PD cases are sporadic in nature, however familial cases account for 5-10% of total PD cases world-wide. The hallmark …

Somatosensory Dysfunction Is Masked By Variable Cognitive Deficits Across Patients On The Alzheimer’S Disease Spectrum, Alex I. Wiesman, Victoria M. Mundorf, Chloe C. Casagrande, Sara L. Wolfson, Craig M. Johnson, Pamela E. May, Daniel L. Murman, Tony W. Wilson

Center for Brain, Biology, and Behavior: Faculty Publications

Background: Alzheimer’s disease (AD) is generally thought to spare primary sensory function; however, such interpretations have drawn from a literature that has rarely taken into account the variable cognitive declines seen in patients with AD. As these cognitive domains are now known to modulate cortical somato-sensory processing, it remains possible that abnormalities in somatosensory function in patients with AD have been suppressed by neuropsychological variability in previous research. Methods: In this study, we combine magnetoencephalographic (MEG) brain imaging during a paired-pulse somatosensory gating task with an extensive battery of neuropsychological tests to investigate the influence of cognitive variability on estimated …

The Role Of Vps54 In Drosophila Melanogaster Neuronal Development And Age Progressive Neurodegeneration, Emily Wilkinson

Electronic Theses and Dissertations

Vps54 is a subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to the trans-Golgi network (TGN). The “wobbler” mouse is the phenotypic result of a destabilizing point mutation in Vps54. This mutation causes neurodegeneration and is subsequently used as a model for human motor neuron disease. Presently, it is unclear how disruption of GARP complex function leads to motor neuron degeneration. To better understand the role of Vps54 in motor neuron development, function, and age-related neurodegeneration, we disrupted expression of the Vps54 ortholog in Drosophila and examined the impact on larval neuromuscular junction …