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Methodological Advances For Studying Gamma Motor Neurons, Katherine A. Wilkinson 2021 San Jose State University

Methodological Advances For Studying Gamma Motor Neurons, Katherine A. Wilkinson

Faculty Publications, Biological Sciences

The muscle spindle is an important sense organ for motor control and proprioception. Specialized intrafusal fibers are innervated by both stretch sensitive afferents and γ motor neurons that control the length of the spindle and tune the sensitivity of the muscle spindle afferents to both dynamic movement and static length. γ motor neurons share many similarities with other skeletal motor neurons, making it challenging to identify and specifically record or stimulate them. This short review will discuss recent advances in genetic and molecular biology techniques, electrophysiological recording, optical imaging, computer modelling, and stem cell culture techniques that have the potential ...


Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich 2021 The Graduate Center, City University of New York

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 ...


Influence Of Demographic, Clinical, And Neuroimaging Variables On Neuropsychological Recovery Trajectories After Moderate-To-Severe Traumatic Brain Injury, Elizabeth J. Leif 2021 The Graduate Center, City University of New York

Influence Of Demographic, Clinical, And Neuroimaging Variables On Neuropsychological Recovery Trajectories After Moderate-To-Severe Traumatic Brain Injury, Elizabeth J. Leif

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is prevalent in people of all ages and all walks of life. Cognitive deficits are common after TBI and the recovery patterns are known to be variable across individuals. The current study investigates diffuse axonal injury (DAI), cerebral blood flow (CBF), and focal lesions, in addition to post-traumatic amnesia (PTA), as possible predictors of cognitive trajectory in moderate-to-severe TBI patients. Cognitive trajectory was evaluated with a battery of neuropsychological tests that were combined into three domains: processing speed, verbal learning, and executive function. Patients (N=44) were tested three times at 3, 6, and 12 months ...


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 2021 Wayne State University

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 ...


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 2021 University of Kentucky

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 ...


Glial Cell Dysfunction In C9orf72-Related Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Mehdi Ghasemi, Kiandokht Keyhanian, Catherine Douthwright 2021 University of Massachusetts Medical School

Glial Cell Dysfunction In C9orf72-Related Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Mehdi Ghasemi, Kiandokht Keyhanian, Catherine Douthwright

Open Access Publications by UMMS Authors

Since the discovery of the chromosome 9 open reading frame 72 (C9orf72) repeat expansion mutation in 2011 as the most common genetic abnormality in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) and frontotemporal dementia (FTD), progress in understanding the signaling pathways related to this mutation can only be described as intriguing. Two major theories have been suggested-(i) loss of function or haploinsufficiency and (ii) toxic gain of function from either C9orf72 repeat RNA or dipeptide repeat proteins (DPRs) generated from repeat-associated non-ATG (RAN) translation. Each theory has provided various signaling pathways that potentially participate in ...


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 2021 University of Cincinnati

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

NeuroSports

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 12 ...


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 2021 Michigan State University

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 Publications

© 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 biocompatibility ...


Neuronal Post-Developmentally Acting Sax-7s/L1cam Can Function As Cleaved Fragments To Maintain Neuronal Architecture In C. Elegans [Preprint], Virginie E. Desse, Cassandra R. Blanchette, Paola N. Perrat, Claire Y. Benard 2021 Université du Québec à Montréal

Neuronal Post-Developmentally Acting Sax-7s/L1cam Can Function As Cleaved Fragments To Maintain Neuronal Architecture In C. Elegans [Preprint], Virginie E. Desse, Cassandra R. Blanchette, Paola N. Perrat, Claire Y. Benard

University of Massachusetts Medical School Faculty Publications

Whereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal’s growth, maturation processes, the addition of new neurons, body movements, and aging. The C. elegans protein SAX-7, homologous to the vertebrate L1 protein family, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function of sax-7 in neuronal maintenance, we generated a null allele and ...


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 2021 University of Nevada, Las Vegas

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 Publications

© 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 2021 UT Southwestern Medical Center, Dallas, USA.

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 ...


Htt Is A Repressor Of Abl Activity Required For App-Induced Axonal Growth, Claire Marquilly, Germain U. Busto, Brittany S. Leger, Ana Boulanger, Edward Giniger, James A. Walker, Lee G. Fradkin, Jean-Maurice Dura 2021 University of Montpellier

Htt Is A Repressor Of Abl Activity Required For App-Induced Axonal Growth, Claire Marquilly, Germain U. Busto, Brittany S. Leger, Ana Boulanger, Edward Giniger, James A. Walker, Lee G. Fradkin, Jean-Maurice Dura

Open Access Publications by UMMS Authors

Huntington's disease is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine tract at the N-terminus of a large cytoplasmic protein. The Drosophila huntingtin (htt) gene is widely expressed during all developmental stages from embryos to adults. However, Drosophila htt mutant individuals are viable with no obvious developmental defects. We asked if such defects could be detected in htt mutants in a background that had been genetically sensitized to reveal cryptic developmental functions. Amyloid precursor protein (APP) is linked to Alzheimer's disease. Appl is the Drosophila APP ortholog and Appl signaling modulates axon outgrowth ...


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 2021 Neurodegenerative Disease Research Group

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 Publications

© 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 ...


Deletions In Cwh43 Cause Idiopathic Normal Pressure Hydrocephalus, Hong Wei Yang, Dejun Yang, Huijun Dai, Yan Zhang, Sijun Zhao, Shuo Zhang, Yan Ma, George Wang, Shaokuan Zheng, Rona S. Carroll, Mark D. Johnson 2021 University of Massachusetts Medical School

Deletions In Cwh43 Cause Idiopathic Normal Pressure Hydrocephalus, Hong Wei Yang, Dejun Yang, Huijun Dai, Yan Zhang, Sijun Zhao, Shuo Zhang, Yan Ma, George Wang, Shaokuan Zheng, Rona S. Carroll, Mark D. Johnson

Radiology Publications

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6-fold and 2.7-fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol-anchored proteins. Mice heterozygous for CWH43 deletion appeared ...


Genetic Analysis Of Amyotrophic Lateral Sclerosis Identifies Contributing Pathways And Cell Types, Sara Saez-Atienzar, John E. Landers 2021 National Institutes of Health

Genetic Analysis Of Amyotrophic Lateral Sclerosis Identifies Contributing Pathways And Cell Types, Sara Saez-Atienzar, John E. Landers

Open Access Publications by UMMS Authors

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq ...


Internal And External Challenges To Culpability, Stephen J. Morse 2021 University of Pennsylvania Carey Law School

Internal And External Challenges To Culpability, Stephen J. Morse

Faculty Scholarship at Penn Law

This article was presented at “Guilty Minds: A Virtual Conference on Mens Rea and Criminal Justice Reform” at Arizona State University’s Sandra Day O’Connor College of Law. It is forthcoming in Arizona State Law Journal Volume 53, Issue 2.

The thesis of this article is simple: As long as we maintain the current folk psychological conception of ourselves as intentional and potentially rational creatures, as people and not simply as machines, mental states will inevitably remain central to ascriptions of culpability and responsibility more generally. It is also desirable. Nonetheless, we are in a condition of unprecedented internal ...


Keeping Weight Off: Mindfulness-Based Stress Reduction Alters Amygdala Functional Connectivity During Weight Loss Maintenance In A Randomized Control Trial, Serhiy Y. Chumachenko, Ryan J. Cali, Milagros C. Rosal, Jeroan J. Allison, Sharina D. Person, Douglas Ziedonis, Ben Nephew, Constance M. Moore, Nanyin Zhang, Jean A. King, Carl E. Fulwiler 2021 University of Massachusetts Medical School

Keeping Weight Off: Mindfulness-Based Stress Reduction Alters Amygdala Functional Connectivity During Weight Loss Maintenance In A Randomized Control Trial, Serhiy Y. Chumachenko, Ryan J. Cali, Milagros C. Rosal, Jeroan J. Allison, Sharina D. Person, Douglas Ziedonis, Ben Nephew, Constance M. Moore, Nanyin Zhang, Jean A. King, Carl E. Fulwiler

Population and Quantitative Health Sciences Publications

Obesity is associated with significant comorbidities and financial costs. While behavioral interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. The objective was to improve understanding of the neural and psychological mechanisms modified by mindfulness that may predict clinical outcomes. Individuals who intentionally recently lost weight were randomized to Mindfulness-Based Stress Reduction (MBSR) or a control healthy living course. Anthropometric and psychological factors were measured at baseline, 8 weeks and 6 months. Functional connectivity (FC) analysis was performed at baseline and 8 weeks to examine FC changes between regions of interest selected a priori, and independent components identified ...


Apathy And Striatal Gray Matter Patterns In Schizophrenia And Huntington’S Disease, Gabriel Martinez, Skylar Walters, J S. Paulsen, Vince Calhoun, Jessica Turner 2021 Georgia State University

Apathy And Striatal Gray Matter Patterns In Schizophrenia And Huntington’S Disease, Gabriel Martinez, Skylar Walters, J S. Paulsen, Vince Calhoun, Jessica Turner

Neuroscience Institute Faculty Publications

Apathy is a symptom of many neurodegenerative and neuropsychiatric disorders, such as Huntington's disease and schizophrenia. Apathy is often conceptualized as a combination of three domains, cognitive, behavioral, and emotional, characterized by impaired goal-directed behavior. The striatum has been shown to be significantly associated with executive functions and planned motor behavior via projection to the prefrontal cortex (PFC). Due to its connection to the PFC and its involvement in the basal ganglia motor circuit, the striatum is thought to be a significant part of the circuit that controls goal-directed behavior. The purpose of this study was to investigate the ...


Cognitive Abilities In Hearing Loss: Perceived And Performance Abilities Of Adults Related To Attention, Memory, And Social Cognition, Karah Gottschalk 2021 University of Kentucky

Cognitive Abilities In Hearing Loss: Perceived And Performance Abilities Of Adults Related To Attention, Memory, And Social Cognition, Karah Gottschalk

Theses and Dissertations--Gerontology

Hearing loss is the most common sensory deficit noted in aging adults. It is commonly known to reduce an individual’s ability to detect, identify, and localize sounds and speech and to cause issues in communication. However, there are other less commonly discussed impacts that hearing loss has beyond the auditory system. Literature suggests a correlation between hearing loss and cognition in aging adults. Similar to hearing loss, the domains of cognition experience performance and functional changes across the life span. In an aging adult, changes related to cognition are also suggested to be associated with hearing loss. This study ...


Network And Cellular Effects Of The Mu Opioid Receptor In Cortical Interneurons, Adrian Dutkiewicz 2021 University of Vermont

Network And Cellular Effects Of The Mu Opioid Receptor In Cortical Interneurons, Adrian Dutkiewicz

Graduate College Dissertations and Theses

The µ opioid receptor (µOR) exerts a powerful excitatory effect in cortical circuits and cultured neurons by promoting glutamatergic activity after binding endogenous or exogenous opioids. While most research indicates that the receptor does this by decreasing activity or output of GABAergic interneurons that inhibit glutamate-releasing Pyramidal Neurons, other experiments suggest that the µOR directly upregulates excitatory Pyramidal Neurons instead. Thus, the cellular target of cortical opioid agonists remains unclear, and the µOR’s net excitatory mechanisms are not fully understood. Consequently, utilizing electrophysiology to detect µOR responses to the specific agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) has yielded incomplete ...


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