Neuroscience and Neurobiology Commons^™

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 …

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 …

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 …

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. …

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 …

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 …

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 …

P24. The Birds And The Beats: Perception Of A Beat In An Avian Model, Brendon Samuels

Western Research Forum

Background: Beat perception is a complex cognitive skill that enables humans to “feel” the beat in music, and is an essential component of synchronization of behavior and dance. The mechanisms in the human brain that facilitate beat perception are not entirely understood, and have only been studied thus far using non-invasive techniques. Some animals, such as songbirds, also seem to be able to detect a beat in rhythms, though this has never been formally tested independent of motor synchronization.

Methods: An operant experiment is used to assess if European starlings, a type of songbird, are capable of categorizing …

P27. Acute Impact Of An Extremely Low Frequency Magnetic Stimulus On Human Neurophysiological Function - Magnetophosphene Perception, Cadence M. Baker

Western Research Forum

Background: Magnetophosphenes are classified as colourless, flickering lights that are perceived with closed eyes in the dark, and upon exposure to a magnetic field (MF). Uncertainties exist involving the MF threshold for magnetophosphene perception.

Methods: Forty subjects will be enrolled in this experiment aiming to provide a frequency-response curve of magnetophosphene perception under MF exposure. Subjects will sit in a whole head MF exposure device wearing a 64-channel MRI-compatible EEG cap. Subjects will be exposed to a MF with a frequency of 5-300 Hz, in the form of an increasing flux density ramp (increasing magnetic field flux density from 0-100 …

P30. Optimizing Current Steering In Deep Brain Stimulation For Treating Parkinsonian Axial Motor Symptoms, Daphne Hui

Western Research Forum

Background: The proposed study will investigate deep brain stimulation (DBS), of the subthalamic nucleus (STN) to improve gait dysfunctions in advanced Parkinson’s Disease (PD). DBS requires implantation of electrodes into the brain that contain contacts where current traverses to stimulate neurons. Imprecise electrode implantations are inherent in surgical implantation; thus, contributing to the elusiveness of DBS on gait.

Methods: The proposed investigation will divide current between two contacts to receive 0, 30, 50, 70, or 100% of current, to find the best combination to improve gait. Gait changes associated with fractional combinations will be visually assessed with clinical scales, and …

P32. Altered Sensory Processing In Response To Novel Dreadd-Induced Inactivation Of Gaba In Pedunculopontine Tegmental Nucleus, Niveen Fulcher

Western Research Forum

Niveen Fulcher¹, Cleusa De Oliveira², & Susanne Schmid^1,2

¹Schulich School of Medicine & Dentistry, University of Western Ontario

²Anatomy and Cell Biology, University of Western Ontario

Altered sensory processing in response to novel DREADD-induced inactivation of GABA in pedunculopontine tegmental nucleus

Background: Sensory processing deficits are associated with certain psychiatric illnesses, such as schizophrenia and autism spectrum disorder (ASD). Sensory filtering and sensorimotor gating are evolutionarily conserved preattentive responses that filter and block redundant sensory stimuli that would otherwise overwhelm our brains. To date, underlying mechanisms of these deficits are undefined. Prepulse …

P34. The Effects Of Standing Desks On Classroom Performance Of University Students, Siobhan Smith

Western Research Forum

Background:

It is well established that there are many health risks associated with prolonged sedentary time.¹ Unfortunately, research conducted on university students is limited but yet they experience excessive periods of sitting time during class and while studying.

Methods:

Recently, we investigated the effect of sitting, dynamic sitting, and standing desks on classroom performance of university students.² Participants performed three 3-minute classroom simulations, one for each of the three desks. The order of the desks and simulations were randomized. Each of the simulations included a different typing and memory task.

Results:

Results showed no significant difference in the …

P35. Investigating The Effect Of Maternal Immune Activation On Sensory Filtering, Social Behaviour And Attention, Faraj Haddad

Western Research Forum

Background

Altered brain development is associated with many neuropsychiatric disorders like Autism Spectrum Disorder (ASD) and schizophrenia. Environmental insults can interfere with neurodevelopment, and a prominent example is maternal infection during pregnancy. Epidemiological studies show that children born to mothers who were infected during pregnancy display a higher risk of developing ASD and schizophrenia, and this effect is mainly due to the maternal immune response. Polyinosinic-polycytidilic acid (Poly I:C) is a double stranded RNA molecule that mimics viral markers and elicits an immune response. When injected in pregnant rodents, this model produces offspring that exhibit core symptoms of ASD and …

The Impact Of Various Predator Perceptions On Stress Response And Spatial Memory In Birds, Chlöe S. N. Carter

Western Research Forum

The Impact of Various Predator Perceptions on Stress Response and Spatial Memory in Birds

Background

This project will explore the impact of environmental stressors on the cognitive abilities of birds. Predator perception has been demonstrated to elicit a stress response by elevating stress hormones which can alter the behaviour of birds. The aim of this study is to observe if chronic stress from differently perceived threats of predation in an individual’s environment will lead to differences in the spatial memory abilities in two species of birds. I predict that chronic stress resulting from predator stimuli will impair the bird’s performance …

Eeg In The Classroom: Synchronised Neural Recordings During Video Presentation, Andreas Trier Poulsen, Simon Kamronn, Jacek Dmochowski, Lucas C. Parra, Lars Kai Hansen

Publications and Research

We performed simultaneous recordings of electroencephalography (EEG) from multiple students in a classroom, and measured the inter-subject correlation (ISC) of activity evoked by a common video stimulus. The neural reliability, as quantified by ISC, has been linked to engagement and attentional modulation in earlier studies that used high-grade equipment in laboratory settings. Here we reproduce many of the results from these studies using portable low-cost equipment, focusing on the robustness of using ISC for subjects experiencing naturalistic stimuli. The present data shows that stimulusevoked neural responses, known to be modulated by attention, can be tracked for groups of students with …

Beta Oscillatory Changes And Retention Of Motor Skills During Practice In Healthy Subjects And In Patients With Parkinson’S Disease, Aaron B. Nelson, Clara Moisello, Jing Lin, Priya Panday, Serena Ricci, Andrea Canessa, Alessandro Di Rocco, Angelo Quartarone, Giuseppe Frazzitta, Ioannis U. Isaias, Giulio Tononi, Chiara Cirelli, M. Felice Ghilardi

Publications and Research

Recently we found that modulation depth of beta power during movement increases with practice over sensory-motor areas in normal subjects but not in patients with Parkinson’s disease (PD). As such changesmight reflect use-dependentmodifications, we concluded that reduction of beta enhancement in PD represents saturation of cortical plasticity. A few questions remained open: What is the relation between these EEG changes and retention of motor skills? Would a second task exposure restore beta modulation enhancement in PD? Do practice-induced increases of beta modulation occur within each block? We thus recorded EEG in patients with PD and age-matched controls in two consecutive …

Neurophysiological And Behavioral Responses Of Mandarin Lexical Tone Processing, Yan H. Yu, Valerie L. Shafer, Elyse S. Sussman

Publications and Research

Language experience enhances discrimination of speech contrasts at a behavioral- perceptual level, as well as at a pre-attentive level, as indexed by event-related potential (ERP) mismatch negativity (MMN) responses. The enhanced sensitivity could be the result of changes in acoustic resolution and/or long-term memory representations of the relevant information in the auditory cortex. To examine these possibilities, we used a short (ca. 600 ms) vs. long (ca. 2,600 ms) interstimulus interval (ISI) in a passive, oddball discrimination task while obtaining ERPs. These ISI differences were used to test whether cross-linguistic differences in processing Mandarin lexical tone are a function of …

Genetic Variants Contributing To Frontotemporal Dementia With Parkinsonism, Elizabeth C. Oduwo

UNO Student Research and Creative Activity Fair

Frontotemporal dementia with parkinsonism (FTDP) is a neurodegenerative disease characterized by disturbances in cognition, language, and personality, which also has features of parkinsonism. This disease is associated with multiple genes including two located close together on chromosome 17: MAPT and GRN. Human and medical genetics can be used to identify the genes that contribute to the risk of this disease.

Earlier work in the Chase lab had identified a large Mennonite kindred (MEN-1) where parkinsonism and dementia were found in five members of a nuclear family. These symptoms parallel those seen in FTDP and all of the affected members share …

Movement Variability And Sensorimotor Cortical Activation During Forward And Backward Walking, Boman Groff

UNO Student Research and Creative Activity Fair

Previous research has used functional near-infrared spectroscopy (fNIRS) to show that motor areas of the cortex are activated more while walking backward compared to walking forward. It is also known that head movement creates motion artifacts in fNIRS data. The aim of this study was to expand on previous findings by examining cortical activation during forward and backward walking, while also measuring head movement. We hypothesized that greater activation in motor areas while walking backward would be concurrent with increased head movement.

Participants (N=8) performed forward and backward walking on a treadmill. Participants wore motion capture markers on their head …

Differences In Behavioral Responses To Stress In Zebrafish: Exploring Underlying Neural Mechanisms, Jacalyn B. Russ

UNO Student Research and Creative Activity Fair

Two alternative “stress coping styles” are documented across a wide range of taxa: proactive and reactive. While behavior differences can be observed between coping styles, brain regions potentially mediating these differences have not been studied extensively. Understanding differences in how the brain processes information between the coping styles can lead to insights on how these responses might be controlled. To assess the neural mechanisms underlying alternative stress coping styles, I utilized Danio rerio (zebrafish) and the Novel Tank Diving Test (NTDT). I hypothesize (i) that proactive fish will spend less time in the lower portion of the NTDT and spend …

Comparing Consistency Of Stress And Anxiety-Related Behaviors Across Time In Zebrafish (Danio Rerio), Matthew R. Baker, Alex Goodman

UNO Student Research and Creative Activity Fair

Animals are frequently faced with stressors in their environment that they must overcome to survive and reproduce. Across vertebrates, two distinct stress coping styles or ‘personalities’ have been observed known as proactive (bold) and reactive (shy). Animal personalities may be advantageous by limiting individual variation and balancing different trade-offs in unpredictable environments. When identifying animal personalities, behavioral phenotypes must be consistent and repeatable across contexts and time. Here we use selectively bred lines of shy and bold zebrafish, previously shown to have consistent divergent fear- and anxiety-related behaviors across contexts, to test the repeatability and consistency of these behaviors across …

Assessment Of Olfactory-Based Social Recognition: Designing A Paradigm For Marmosets, Stephanie Womack

UNO Student Research and Creative Activity Fair

Navigation of the social world depends largely on one’s responsiveness to social stimuli and information from a wide range of senses can be used to discriminate between individuals. Mammals use several sensory modes to communicate and respond to their surroundings, but olfaction is the dominant sense across most species. Chemosignals provide a wealth of information including sex, age, reproductive status, and individual identity. Currently, assessment of olfaction is largely limited to the habituation-dishabituation paradigm or the two-choice discrimination task used primarily in rodents. These paradigms are limited by their reliance on inherent reward of interaction with stimuli without providing additional …

The Effect Of Observing Aggressive Interactions On The Personality Traits Of Danio Rerio, Jessica L. Bargstadt

UNO Student Research and Creative Activity Fair

Social animals are easily influenced by other members of their species. Individuals will adjust their behaviors and actions both when observing another conspecific and when interacting with one. The effect that these social experiences can have on an individual vary in both magnitude and permanence, depending on the type of experience. We seek to examine the lasting effect that observing an aggressive interaction can have on the personality type of an individual.

Personality traits of Danio rerio will be examined in a novel environment setting in which the subject’s movements are recorded to determine their reactivity or proactivity in response …

Spatial And Temporal High Processing Of Visual And Auditory Stimuli In Cervical Dystonia, Gaetana Chillemi, Alessandro Calamuneri, Francesca Morgante, Carmen Terranova, Vincenzo Rizzo, Paolo Girlanda, Maria Felice Ghilardi, Angelo Quartarone

Publications and Research

Objective: Investigation of spatial and temporal cognitive processing in idiopathic cervical dystonia (CD) by means of specific tasks based on perception in time and space domains of visual and auditory stimuli.

Background: Previous psychophysiological studies have investigated temporal and spatial characteristics of neural processing of sensory stimuli (mainly somatosensorial and visual), whereas the definition of such processing at higher cognitive level has not been sufficiently addressed. The impairment of time and space processing is likely driven by basal ganglia dysfunction. However, other cortical and subcortical areas, including cerebellum, may also be involved.

Methods: We tested 21 subjects with CD and …

Higher-Order Power Harmonics Of Pulsed Electrical Stimulation Modulates Corticospinal Contribution Of Peripheral Nerve Stimulation, Chiun-Fan Chen, Marom Bikson, Li-Wei Chou, Chunlei Shan, Niranjan Khadka, Wen-Shiang Chen, Felipe Fregni

Engineering Science Faculty Publications

It is well established that electrical-stimulation frequency is crucial to determining the scale of induced neuromodulation, particularly when attempting to modulate corticospinal excitability. However, the modulatory effects of stimulation frequency are not only determined by its absolute value but also by other parameters such as power at harmonics. The stimulus pulse shape further influences parameters such as excitation threshold and fiber selectivity. The explicit role of the power in these harmonics in determining the outcome of stimulation has not previously been analyzed. In this study, we adopted an animal model of peripheral electrical stimulation that includes an amplitude-adapted pulse train …