Neurosciences Commons^™

Global Connectivity And Function Of Descending Spinal Input Revealed By 3d Microscopy And Retrograde Transduction, Zimei Wang, Brian Maunze, Yunfang Wang, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The brain communicates with the spinal cord through numerous axon tracts that arise from discrete nuclei, transmit distinct functions, and often collateralize to facilitate the coordination of descending commands. This complexity presents a major challenge to interpreting functional outcomes from therapies that target supraspinal connectivity after injury or disease, while the wide distribution of supraspinal nuclei complicates the delivery of therapeutics. Here we harness retrograde viral vectors to overcome these challenges. We demonstrate that injection of AAV2-Retro to the cervical spinal cord of adult female mice results in highly efficient transduction of supraspinal populations throughout the brainstem, midbrain, and cortex. …

Impaired Object-Location Learning And Recognition Memory But Enhanced Sustained Attention In M2 Muscarinic Receptor-Deficient Mice, Carola Romberg, Susan Bartko, Jürgen Wess, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood. Objectives: The aim of this study was to investigate the contribution of M2-type muscarinic receptor signalling to sustained attention, executive control and learning and memory. Methods: M2 receptor-deficient (M2−/−) mice were tested on a touchscreen-operated task battery testing visual discrimination, behavioural flexibility, object-location associative learning, attention and response control. Spontaneous …

The Psychological Science Accelerator: Advancing Psychology Through A Distributed Collaborative Network, Hannah Moshontz, Lorne Campbell, Charles R. Ebersole, Hans Ijzerman, Heather L. Urry, Patrick S. Forscher, Jon E. Grahe, Randy J. Mccarthy, Erica D. Musser, Jan Antfolk, Christopher M. Castille, Thomas Rhys Evans, Susann Fiedler, Jessica Kay Flake, Diego A. Forero, Steve M. Janssen, Justin Robert Keene, John Protzko, Balazs Aczel, Sara Álvarez Solas, Daniel Ansari, Dana Awlia, Ernest Baskin, Carlota Batres, Martha Lucia Borras-Guevara, Cameron Brick, Priyanka Chandel, Armand Chatard, William J. Chopik, David Clarance, Nicholas A. Coles, Katherine S. Corker

Brain and Mind Institute Researchers' Publications

Concerns have been growing about the veracity of psychological research. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions, or attempt to replicate prior …

The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis

Electronic Theses and Dissertations

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …

Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar

Farber Institute for Neuroscience Faculty Papers

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of …

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta

School of Medicine Faculty Publications

No abstract provided.

Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker

USF Tampa Graduate Theses and Dissertations

The negative health and economic impacts of neurodegenerative diseases on Americans is astounding and accelerating with an aging population. The Alzheimer’s Association reports that 5.7 million Americans suffer from Alzheimer’s disease (AD), a number which is expected to increase to 14 million by 2050. In economic terms, AD and other neurodegenerative disorders will cost the US over $275 billion in 2018, rising to over $1 trillion annually by 2050. AD causes gross brain atrophy and is most damaging throughout the cortex and the hippocampus, regions required for higher cognitive function and memory. AD presents as tangles within neurons composed of …

Proteolysis Of Cx3cl1 Impacts Cx3cr1 Signaling And Therapeutic Benefits In A Tauopathy Model, Dylan John Finneran

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder and the most common form of dementia. The hallmark pathologies of AD are extracellular aggregates of amyloid-beta, intracellular aggregates of microtubule associated protein tau and increased neuroinflammation. Current therapeutics offer only symptomatic relief and clinical trials investigating therapeutic benefits of non-steroidal anti-inflammatory drugs have yielded no positive results. Therefore, recent work has focused on immunomodulators, such as CD200 and fractalkine, as potential therapeutic targets for AD.

Fractalkine (CX3CL1; FKN) is expressed as a transmembrane protein with an N-terminal chemokine domain followed by a long, mucin-like stalk. FKN can signal as a membrane-bound …

Demonstration Of Monolithic-Silicon Carbide (Sic) Neural Devices, Evans K. Bernardin

USF Tampa Graduate Theses and Dissertations

Brain Machine Interfaces (BMI) provide a communication pathway between the electrical conducting units of the brain (neurons) and external devices. BMI technology may provide improved neurological and physiological functions to patients suffering from disabilities due to damaged nervous systems. Unfortunately, microelectrodes used in Intracortical Neural Interfaces (INI), a subset of the BMI device family, have yet to demonstrate long-term in vivo performance due to material, mechanical and electrical failures. Many state-of-the-art INI devices are constructed using stacks of multiple materials, such as silicon (Si), titanium (Ti), platinum (Pt), parylene C, and polyimide. Not only must each material tolerate the biological …

Lateral Position And Utility Of Navigation For Posterior Fixation Of Unstable Cervical Fracture With Ankylosing Spondylitis., Zubair Ahammad, Jason Milton, Kailash Narayan, Victor Awuor

Neuroscience Articles

BACKGROUND: Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy within the spectrum of rheumatologic diseases. The systemic inflammation that characterizes AS leads to bone resorption and reformation. Pathologic remodeling may include kyphosis, osteoporosis, and multi-segment auto-fusion. Cervical fractures account for 53-78% of spinal trauma seen with AS. Surgical planning is often challenging owing to spinal deformity, medical comorbidities, the cervicothoracic foci of injury, and gross instability of these fracture.

CASE DESCRIPTION: A 55-year-old male with AS was presented with a three-column injury at the C6 level. The C6 vertebra was fractured, minimally displaced, and there was a focal kyphotic deformity. Attempted …

Leveling The Playing Field: Supporting Neurodiversity Via Virtual Realities, Louanne E. Boyd, Kendra Day, Natalia Stewart, Kaitlyn Abdo, Kathleen Lamkin, Erik J. Linstead

Mathematics, Physics, and Computer Science Faculty Articles and Research

Neurodiversity is a term that encapsulates the diverse expression of human neurology. By thinking in broad terms about neurological development, we can become focused on delivering a diverse set of design features to meet the needs of the human condition. In this work, we move toward developing virtual environments that support variations in sensory processing. If we understand that people have differences in sensory perception that result in their own unique sensory traits, many of which are clustered by diagnostic labels such as Autism Spectrum Disorder (ASD), Sensory Processing Disorder, Attention-Deficit/Hyperactivity Disorder, Rett syndrome, dyslexia, and so on, then we …

Longitudinal Screening Detects Cognitive Stability And Behavioral Deterioration In Als Patients, Susan Woolley, Ray Goetz, Pam Factor-Litvak, Jennifer Murphy, Jonathan Hupf, Catherine Lomen-Hoerth, Howard Andrews, Daragh Heitzman, Richard Bedlack, Jonathan Katz, Richard Barohn, Eric Sorenson, Bjorn Oskarsson, Americo Fernandes Filho, Edward J. Kasarskis, Tahseen Mozaffar, Sharon Nations, Andrea Swenson, Agnes Koczon-Jaremko, Georgia Christodoulou, Hiroshi Mitsumoto

Neurology Faculty Publications

Objective. To evaluate longitudinal cognitive/behavioral change over 12 months in participants enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS). Methods. We analyzed data from 294 ALS participants, 134 of whom were studied serially. Change over time was evaluated controlling for age, sex, symptom duration, education, race, and ethnicity. Using multiple regression, we evaluated associations among decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and cognitive/behavioral changes. Change in cognitive/behavioral subgroups was assessed using one-way analyses of covariance. Results. Participants with follow-up data had fewer baseline behavior problems compared to patients …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

The Effect Of Energy-Matched Exercise Intensity On Brain-Derived Neurotrophic Factor And Motor Learning, Jessica F. Baird, Mary E. Gaughan, Heath M. Saffer, Mark A. Sarzynski, Troy M. Herter, Stacy L. Fritz, Dirk B. Den Ouden, Jill Campbell Stewart

Communication Sciences and Disorders Faculty Articles and Research

Background

Methods

Common Sense And Common Nonsense: A Conversation About Mental Attitudes, Science, And Society, Daniel S. Levine

Psychology Faculty Publications - Archive

Daniel S. Levine's Common Sense and Common Nonsense observes human decision making, ethics, and social organization as illuminated by the scientific disciplines of neural network theory, neuroscience, experimental psychology, and dynamical systems theory. It is a book whose aim is advocacy as well as research. Its goal is to use an understanding of our brains and minds to better operationalize Aldous Huxley's admonition to "try to be a little kinder." It wanders over examples from sociology, politics, economics, religion, literature, and many other fields but looks at all as examples of a few common themes. The "common nonsense" of the …

Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Pedronel Araque, Richard M. Ransohoff, Astrid E. Cardona

Department of Microbiology and Immunology Faculty Papers

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During …

How Concussions Alter Brain Network Properties: Towards Better Diagnoses Of Concussions, Sara Krehbiel, Joanna R. Wares

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Developmental Chromatin Restriction Of Pro‐Growth Gene Networks Acts As An Epigenetic Barrier To Axon Regeneration In Cortical Neurons, Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age‐dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome‐wide maps of chromatin accessibility. When applied …

Coordination Of Inpatient And Outpatient Care For Neurology Patients Undergoing Epilepsy Monitoring, Sara Schrock, Michelle Beane, Kathryn Cope, Mark Parker, Suneela Nayak, Ruth Hanselman, Stephen Tyzik, Amy Sparks, Brendan Lilley

Operations Transformation

ORGANIZING A SYSTEM TO CONSOLIDATE EPILEPSY REFERRALS TO AN OUTPATIENT NEUROLOGY PRACTICE

An outpatient neurology practice was experiencing delayed or lost referrals for epilepsy monitoring. This delay was leading many patients to suffer unnecessary and unmanaged seizures and, in some cases, frequent trips to the emergency department.

As a result, a team consisting of the neurology practice and neuro-navigators used baseline metrics to demonstrate the current state of the problem and conducted a root cause analysis that outlined several causes. A number of countermeasures were initiated with the goal of decreasing referral misses.

Post the initiation of two KPIs, a …

Changes In Electroencephalogram Coherence In Adolescents With Autism Spectrum Disorder After A Social Skills Intervention, Angela D. Haendel

Dissertations (1934 -)

Autism spectrum disorder (ASD) is a developmental disorder that affects social communication and behavior. There is a consensus that neurological differences present in individuals with ASD. Further, theories emphasize the mixture of hypo- and hyper-connectivity as a neuropathology in ASD (O’Reilly, Lewis, & Elsabbagh, 2017), however, there is a paucity of studies specifically testing neurological underpinnings as predictors of success on social skills interventions. This study examined functional neural connectivity (electroencephalogram, EEG, coherence) of adolescents with ASD before and after the Program for the Education and Enrichment of Relational Skills (PEERS®) intervention. Two groups were utilized in this randomized controlled …

Translational Evaluation Of Acid/Base And Electrolyte Alterations In Rodent Model Of Focal Ischemia, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Hilary A. Seifert, Christopher C. Leonardo, Craig T. Ajmo, Elspeth A. Foran, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

BACKGROUND AND PURPOSE: Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion.

METHODS: Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient …

Henle's Ligament: A Comprehensive Review Of Its Anatomy And Terminology Over Almost One And A Half Centuries., Raja Gnanadev, Joe Iwanaga, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

Henle's ligament was first described by German physician and anatomist, Friedrich Henle, in 1871. This review article will cover Henle's original description of the ligament, historical changes in terminology, embryological studies of the ligament, and the clinical significance of Henle's ligament. This article has a particular focus on the variation in the terminology of this structure and the implications of this.

New Functions For The Proprioceptive System In Skeletal Biology, Ronen Blecher, Lia Heinemann-Yerushalmi, Eran Assaraf, Nitzan Konstantin, Jens R. Chapman, Timothy C. Cope, Guy S. Bewick, Robert W. Banks, Elazar Zelzer

Neuroscience, Cell Biology & Physiology Faculty Publications

Muscle spindles and Golgi tendon organs (GTOs) are two types of sensory receptors that respond to changes in length or tension of skeletal muscles. These mechanosensors have long been known to participate in both proprioception and stretch reflex. Here, we present recent findings implicating these organs in maintenance of spine alignment as well as in realignment of fractured bones. These discoveries have been made in several mouse lines lacking functional mechanosensors in part or completely. In both studies, the absence of functional spindles and GTOs produced a more severe phenotype than that of spindles alone. Interestingly, the spinal curve phenotype, …

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

Isolation Of Cerebral Capillaries From Fresh Human Brain Tissue, Anika M. S. Hartz, Julia A. Schulz, Brent S. Sokola, Stephanie E. Edelmann, Andrew N. Shen, Ralf G. Rempe, Yu Zhong, Nader El Seblani, Bjoern Bauer

Sanders-Brown Center on Aging Faculty Publications

Understanding blood-brain barrier function under physiological and pathophysiological conditions is critical for the development of new therapeutic strategies that hold the promise to enhance brain drug delivery, improve brain protection, and treat brain disorders. However, studying the human blood-brain barrier function is challenging. Thus, there is a critical need for appropriate models. In this regard, brain capillaries isolated from human brain tissue represent a unique tool to study barrier function as close to the human in vivo situation as possible. Here, we describe an optimized protocol to isolate capillaries from human brain tissue at a high yield and with consistent …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Repetitive Transcranial Electrical Stimulation Induces Quantified Changes In Resting Cerebral Perfusion Measured From Arterial Spin Labeling, Matthew Sherwood, Aaron T. Madaris, Casserly R. Mullenger, R. Andy Mckinley

Neuroscience, Cell Biology & Physiology Faculty Publications

The use of transcranial electrical stimulation (TES) as a method to augment neural activity has increased in popularity in the last decade and a half. The specific application of TES to the left prefrontal cortex has been shown to produce broad cognitive effects; however, the neural mechanisms underlying these effects remain unknown. In this work, we evaluated the effect of repetitive TES on cerebral perfusion. Stimulation was applied to the left prefrontal cortex on three consecutive days, and resting cerebral perfusion was quantified before and after stimulation using arterial spin labeling. Perfusion was found to decrease significantly more in a …

Macrophages But Not Astrocytes Harbor Hiv Dna In The Brains Of Hiv-1-Infected Aviremic Individuals On Suppressive Antiretroviral Therapy, Allen Ko, Guobin Kang, Julian B. Hattler, Hadiza I. Galadima, Junfeng Zhang, Qingsheng Li, Woong-Ki Kim

Community & Environmental Health Faculty Publications

The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and …