Neuroscience and Neurobiology Commons^™

Dynamics Of Motor System Excitability During Auditory Anticipation, Justine Czajka

Undergraduate Honors Theses

The ability to anticipate complex sounds, like words in speech or the beat in music, is an important aspect of human perception. However, the changes of excitability in the motor system during auditory anticipation have not been characterized. Here, we applied single-pulse Transcranial Magnetic Stimulation (TMS) to the primary motor cortex to elicit motor evoked potentials (MEPs) from the first dorsal interosseous muscle, the amplitude of which indexes motor system excitability. Healthy right-handed participants (N = 20) underwent TMS stimulation during listening to regular (periodic) tone sequences at three rates (200ms, 550ms, and 900ms) and irregular tone sequences. We assessed …

Retention Of Normal Glia Function By An Isoform-Selective Protein Kinase Inhibitor Drug Candidate That Modulates Cytokine Production And Cognitive Outcomes, Zhengqiu Zhou, Adam D. Bachstetter, Claudia B. Späni, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates. Therefore, it is essential that the glial effects of this CNS-active kinase inhibitor be addressed in order to anticipate future use in clinical investigations.

Methods: …

Transcranial Magnetic Stimulation To Assess Motor System Excitability Fluctuations During Auditory Anticipation And Beat Perception, Johannes G.P Teselink

Undergraduate Honors Theses

Humans tend to spontaneously move to the regular beat of musical rhythm. Beat perception is the tendency to sense and anticipate the regular time positions (beats) that movements synchronize with. The neural motor system plays an important role in beat perception, but the dynamics of excitability in the motor system associated with beat perception have not been characterized. This project investigated motor system excitability fluctuations using transcranial magnetic stimulation and electromyography during perception of beat-based and non-beat-based rhythms. We applied single-pulse TMS over the left primary motor cortex of healthy participants as they listened to three types of rhythms that …

Motion-Induced Position Shifts Activate Early Visual Cortex, Peter J. Kohler, Patrick Cavanagh, Peter U. Tse

Dartmouth Scholarship

The ability to correctly determine the position of objects in space is a fundamental task of the visual system. The perceived position of briefly presented static objects can be influenced by nearby moving contours, as demonstrated by various illusions collectively known as motion-induced position shifts. Here we use a stimulus that produces a particularly strong effect of motion on perceived position. We test whether several regions-of-interest (ROIs), at different stages of visual processing, encode the perceived rather than retinotopically veridical position. Specifically, we collect functional MRI data while participants experience motion-induced position shifts and use a multivariate pattern analysis approach …

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca²⁺]_i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca²⁺]_i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca²⁺ channels.

Results

In CA3 pyramidal neurons, kainic …

Rod-Shaped Microglia Morphology Is Associated With Aging In 2 Human Autopsy Series, Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

A subtype of microglia is defined by the morphological appearance of the cells as rod-shaped. Little is known about this intriguing cell type, as there are only a few case reports describing rod-shaped microglia in the neuropathological literature. Rod-shaped microglia were shown recently to account for a substantial proportion of the microglia cells in the hippocampus of both demented and cognitively intact aged individuals. We hypothesized that aging could be a defining feature in the occurrence of rod-shaped microglia. To test this hypothesis, two independent series of autopsy cases (total n=168 cases), which covered the adult lifespan from 20 – …

Neuroscience Changes More Than You Can Think, Paul S. Davies, Peter A. Alces

Faculty Publications

In this Essay, we consider the contribution of a startling new book, Law & Neuroscience (L&N), by Owen Jones, Jeffrey Schall, and Francis Shen. It is a law school course book (a genre not often the focus of a scholarly review essay) that supports fundamental inquiry into the relationship between emerging neuroscientific insights and doctrinal conceptions in the law. We believe that the book shifts the paradigm and so may profoundly affect the course of normative evaluation of law. In this Essay, we trace and evaluate the “argument” of the book and suggest ways in which its contribution to the …

The Effects Of Soil Copper Contamination On Earthworm Cholinergic Transmission, Locomotion And Muscle Physiology, Tommaso Meregalli

Senior Theses and Projects

No abstract provided.

Cross-Sectional Analysis Of Cortical Thickness Across The Lifespan, Thomas J. Hum-Hyder

Senior Theses and Projects

An understanding of the normal aging process across the lifespan is important for gaining an understanding the pathophysiological changes that occur in accelerated aging diseases, such as Alzheimer’s Disease Dementia (ADD) and Vascular Dementia (VaD). The present study cross-sectionally analyzed cortical thickness values derived from T1-weighted magnetic resonance images for two large cohorts: Human Connectome Project and the Mayo Clinic Study of Aging. The 897 participants aged between 22-36 from the Human Connectome Project and the 801 participants aged between 52-92 from the Mayo Clinic Study of Aging created a robust cohort of non-demented individuals across the lifespan. We found …

Human Neuroblastoma Adaptation To Cobalt Chloride-Induced Hypoxia, Conor Mcauliffe

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is a frequent characteristic of the solid tumor microenvironment, which occurs when cancer cells lack adequate access to oxygen. By selecting for cells that can adapt to and grow in low oxygen conditions, tumor hypoxia contributes to a more aggressive and invasive cancer phenotype that portends a poor clinical outcome. While many aspects of the cellular response to hypoxia have been explored, the roles of some factors have not been fully explained. Cell signaling factors, including signal transducer and activator of transcription 3 (STAT3), the mu opioid receptor (MOR), and the delta opioid receptor (DOR), as well as changes …

Dynamics Of Motor System Excitability During Auditory Anticipation, Justine Czajka

Undergraduate Honors Posters

The ability to anticipate complex sounds, like words in speech or the beat in music, is an important aspect of human perception. However, the changes of excitability in the motor system during auditory anticipation have not been characterized. Here, we applied single-pulse Transcranial Magnetic Stimulation (TMS) to the primary motor cortex to elicit motor evoked potentials (MEPs) from the first dorsal interosseous muscle, the amplitude of which indexes motor system excitability. Healthy right-handed participants (N = 20) underwent TMS stimulation during listening to regular (periodic) tone sequences at three rates (200ms, 550ms, and 900ms) and irregular tone sequences. We assessed …

Transcriptional Signatures Of Brain Aging And Alzheimer's Disease: What Are Our Rodent Models Telling Us?, Kendra E. Hargis, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

Aging is the biggest risk factor for idiopathic Alzheimer’s disease (AD). Recently, the National Institutes of Health released AD research recommendations that include: appreciating normal brain aging, expanding data-driven research, using open-access resources, and evaluating experimental reproducibility. Transcriptome data sets for aging and AD in humans and animal models are available in NIH-curated, publically accessible databases. However, little work has been done to test for concordance among those molecular signatures. Here, we test the hypothesis that brain transcriptional profiles from animal models recapitulate those observed in the human condition. Raw transcriptional profile data from twenty-nine studies were analyzed to produce …

GabaB Receptor Attenuation Of GabaA Currents In Neurons Of The Mammalian Central Nervous System, Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter

Pathology and Laboratory Medicine Faculty Publications

Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABA_B receptor can suppress the ionotropic GABA_A receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation …

Mechanotransduction Current Is Essential For Stability Of The Transducing Stereocilia In Mammalian Auditory Hair Cells, A. Catalina Vélez-Ortega, Mary J. Freeman, Artur A. Indzhykulian, Jonathan M. Grossheim, Gregory I. Frolenkov

Physiology Faculty Publications

Mechanotransducer channels at the tips of sensory stereocilia of inner ear hair cells are gated by the tension of 'tip links' interconnecting stereocilia. To ensure maximal sensitivity, tip links are tensioned at rest, resulting in a continuous influx of Ca²⁺ into the cell. Here we show that this constitutive Ca²⁺ influx, usually considered as potentially deleterious for hair cells, is in fact essential for stereocilia stability. In the auditory hair cells of young postnatal mice and rats, a reduction in mechanotransducer current, via pharmacological channel blockers or disruption of tip links, leads to stereocilia shape changes and shortening. …

Discovery Of Thienoquinolone Derivatives As Selective And Atp Non-Competitive Cdk5/P25 Inhibitors By Structure-Based Virtual Screening, Arindam Chatterjee, Stephen J. Cutler, Robert J. Doerksen, Ikhlas A. Khan, John S. Williamson

John S. Williamson

Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer’s disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2- …

Neutralizing Anti-Interleukin-1Β Antibodies Reduce Ischemia-Related Interleukin-1Β Transport Across The Blood-Brain Barrier In Fetal Sheep, Aparna Patra, Xiaodi Chen, Grazyna B. Sadowska, Jiyong Zhang, Yow-Pin Lim, James F. Padbury, William A. Banks, Barbara S. Stonestreet

Pediatrics Faculty Publications

Hypoxic ischemic insults predispose to perinatal brain injury. Pro-inflammatory cytokines are important in the evolution of this injury. Interleukin-1β (IL-1β) is a key mediator of inflammatory responses and elevated IL-1β levels in brain correlate with adverse neurodevelopmental outcomes after brain injury. Impaired blood-brain barrier (BBB) function represents an important component of hypoxic-ischemic brain injury in the fetus. In addition, ischemia-reperfusion increases cytokine transport across the BBB of the ovine fetus. Reducing pro-inflammatory cytokine entry into brain could represent a novel approach to attenuate ischemia-related brain injury. We hypothesized that infusions of neutralizing IL-1β monoclonal antibody (mAb) reduce IL-1β transport across …

Hearing On The Fly: The Effects Of Wing Position On Noctuid Moth Hearing, Shira D. Gordon, Elizabeth Klenschi, James F. C. Windmill

Dartmouth Scholarship

The ear of the noctuid moth has only two auditory neurons, A1 and A2, which function in detecting predatory bats. However, the noctuid's ears are located on the thorax behind the wings. Therefore, as these moths need to hear during flight, it was hypothesized that wing position may affect their hearing. The wing was fixed in three different positions: up, flat and down. An additional subset of animals was measured with freely moving wings. In order to negate any possible acoustic shadowing or diffractive effects, all wings were snipped, leaving the proximal-most portion and the wing hinge intact. Results revealed …

Trafficking Receptor Signatures Define Blood Plasmablasts Responding To Tissue-Specific Immune Challenge, Yekyung Seong, Nicole Lazarus, Lusijah Sutherland, Aida Habtezion, Tzvia Abramson, Xiao-Song He, Harry Greenberg, Eugene Butcher

Faculty Publications, Biological Sciences

Antibody-secreting cells are generated in regional lymphoid tissues and traffic as plasmablasts (PBs) via lymph and blood to target sites for local immunity. We used multiparameter flow cytometry to define PB trafficking programs (TPs, combinations of adhesion molecules and chemoattractant receptors) and their imprinting in patients in response to localized infection or immune insults. TPs enriched after infection or autoimmune inflammation of mucosae correlate with sites of immune response or symptoms, with different TPs imprinted during small intestinal, colon, throat, and upper respiratory immune challenge. PBs induced after intramuscular or intradermal influenza vaccination, including flu-specific antibody–secreting cells, display TPs characterized …

Predicting The Knowledge: Recklessness Distinction In The Human Brain, Owen D. Jones, Iris Vilares, Michael J. Wesley, Woo-Young Ahn, Et Al.

Vanderbilt Law School Faculty Publications

Criminal convictions require proof that a prohibited act was performed in a statutorily specified mental state. Different legal consequences, including greater punishments, are mandated for those who act in a state of knowledge, compared with a state of recklessness. Existing research, however, suggests people have trouble classifying defendants as knowing, rather than reckless, even when instructed on the relevant legal criteria.

We used a machine-learning technique on brain imaging data to predict, with high accuracy, which mental state our participants were in. This predictive ability depended on both the magnitude of the risks and the amount of information about those …

Tuning Up The Old Brain With New Tricks: Attention Training Via Neurofeedback, Yang Jiang, Reza Abiri, Xiaopeng Zhao

Sanders-Brown Center on Aging Faculty Publications

Neurofeedback (NF) is a form of biofeedback that uses real-time (RT) modulation of brain activity to enhance brain function and behavioral performance. Recent advances in Brain-Computer Interfaces (BCI) and cognitive training (CT) have provided new tools and evidence that NF improves cognitive functions, such as attention and working memory (WM), beyond what is provided by traditional CT. More published studies have demonstrated the efficacy of NF, particularly for treating attention deficit hyperactivity disorder (ADHD) in children. In contrast, there have been fewer studies done in older adults with or without cognitive impairment, with some notable exceptions. The focus of this …