Neuroscience and Neurobiology Commons^™

Evolution Of Caffeine Biosynthetic Enzymes And Pathways In Flowering Plants, Ruiqi Huang

Dissertations

Convergent evolution generally refers to the independent evolution of similar biological function more than once in unrelated species. Caffeine is thought to have evolved by convergence, and is naturally produced through secondary metabolism in plants to defend against pathogen attack and insect feeding or to attract pollinators. The same caffeine biosynthetic pathway has been elucidated in Camellia (tea) and Coffea (coffee), in which xanthosine is sequentially methylated to caffeine via 7-methylxanthine and theobromine. However, although the same catalysis pathway is used, different (paralogous) enzymes in the SAMT/BAMT/theobromine synthase (SABATH) multigene family are used in the two species. In my dissertation, …

Comparison Of The Long-Term Effect Of Positioning The Cathode In Tdcs In Tinnitus Patients, Sarah Rabau, Giriraj S. Shekhawat, Mohamed Aboseria, Daniel Griepp, Vincent Van Rompaey, Marom Bikson, Paul Van De Heyning

Publications and Research

Objective: Transcranial direct current stimulation (tDCS) is one of the methods described in the literature to decrease the perceived loudness and distress caused by tinnitus. However, the main effect is not clear and the number of responders to the treatment is variable. The objective of the present study was to investigate the effect of the placement of the cathode on the outcome measurements.

Methods: Patients considered for the trial were chronic non-pulsatile tinnitus patients with complaints for more than 3 months and a Tinnitus Functional Index (TFI) score that exceeded 25. The anode was placed on the right …

Neurometabolic And Electrophysiological Changes During Cortical Spreading Depolarization: Multimodal Approach Based On A Lactate-Glucose Dual Microbiosensor Arrays, Cátia F. Lourenço, Ana Ledo, Greg A. Gerhardt, João Laranjinha, Rui M. Barbosa

Center for Microelectrode Technology Faculty Publications

Spreading depolarization (SD) is a slow propagating wave of strong depolarization of neural cells, implicated in several neuropathological conditions. The breakdown of brain homeostasis promotes significant hemodynamic and metabolic alterations, which impacts on neuronal function. In this work we aimed to develop an innovative multimodal approach, encompassing metabolic, electric and hemodynamic measurements, tailored but not limited to study SD. This was based on a novel dual-biosensor based on microelectrode arrays designed to simultaneously monitor lactate and glucose fluctuations and ongoing neuronal activity with high spatial and temporal resolution. In vitroevaluation of dual lactate-glucose microbiosensor revealed an extended linear range, …

Ephrin Receptors, Aiy Interneuron Physiology, And Behavior, Tyler Hill

Master of Science in Integrative Biology Theses

In order to survive, an organism must be able to receive, integrate, and respond to sensory stimuli. However, the cellular basis of sensory perception and response is difficult to study in complex animals such as humans, and is therefore poorly understood. The nematode Caenorhabditis elegans is a relatively simple organism yet displays many distinct behaviors, making it an ideal system to understand the relationship between gene function, cell shape, cell physiology, and behavioral output. Much of the thermosensory and chemosensory information that the nematode receives from its sensory neurons is processed via a pair of interneurons called AIYL and AIYR. …

Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin

Dissertations

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder. There are two characteristic histopathological hallmarks in the brain: senile plaques and neurofibrillary tangles, composed of insoluble aggregates of the amyloids Amyloid-β (Aβ) and tau protein, respectively. These diagnostic markers, though distinctive, are not apparent effectors of AD pathology. Evidence has mounted suggesting smaller soluble aggregates (oligomers) of Aβ or tau are the true drivers of disease progression. This dissertation presents several amyloid biophysics projects. Aggregate biophysical parameters such as weight, shape, and conformation were measured using a range of methodologies, including Multiangle Light Scattering, Dynamic Light Scattering, UV-Circular Dichroism, UV-Fluorescence, Scanning …

Social Context-Dependent Activity In Marmoset Frontal Cortex Populations During Natural Conversations, Samuel U. Nummela, Vladimir Jovanovic, Lisa De La Mothe, Cory T. Miller

Psychological Sciences and Counseling Faculty Research

Communication is an inherently interactive process that weaves together the fabric of both human and nonhuman primate societies. To investigate the properties of the primate brain during active social signaling, we recorded the responses of frontal cortex neurons as freely moving marmosets engaged in conversational exchanges with a visually occluded virtual marmoset. We found that small changes in firing rate (∼1 Hz) occurred across a broadly distributed population of frontal cortex neurons when marmosets heard a conspecific vocalization, and that these changes corresponded to subjects' likelihood of producing or withholding a vocal reply. Although the contributions of individual neurons were …

Deep Long Short-Term Memory Structures Model Temporal Dependencies Improving Cognitive Workload Estimation, Ryan G. Hefron, Brett J. Borghetti, James C. Christensen, Christine M. Schubert Kabban

Faculty Publications

Using deeply recurrent neural networks to account for temporal dependence in electroencephalograph (EEG)-based workload estimation is shown to considerably improve day-to-day feature stationarity resulting in significantly higher accuracy (p < .0001) than classifiers which do not consider the temporal dependence encoded within the EEG time-series signal. This improvement is demonstrated by training several deep Recurrent Neural Network (RNN) models including Long Short-Term Memory (LSTM) architectures, a feedforward Artificial Neural Network (ANN), and Support Vector Machine (SVM) models on data from six participants who each perform several Multi-Attribute Task Battery (MATB) sessions on five separate days spread out over a month-long period. Each participant-specific classifier is trained on the first four days of data and tested using the fifth’s. Average classification accuracy of 93.0% is achieved using a deep LSTM architecture. These results represent a 59% decrease in error compared to the best previously published results for this dataset. This study additionally evaluates the significance of new features: all combinations of mean, variance, skewness, and kurtosis of EEG frequency-domain power distributions. Mean and variance are statistically significant features, while skewness and kurtosis are not. The overall performance of this approach is high enough to warrant evaluation for inclusion in operational systems.

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers, Fei Tang, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against …

Osteopontin Facilitates West Nile Virus Neuroinvasion Via Neutrophil “Trojan Horse” Transport, Amber M. Paul, Dhiraj Acharya, Laurel Duty, E. Ashley Thompson, Linda Le, Dobrivoje S. Stokic, A. Arturo Leis, Fengwei Bai

Publications

West Nile virus (WNV) can cause severe human neurological diseases including encephalitis and meningitis. The mechanisms by which WNV enters the central nervous system (CNS) and host factors that are involved in WNV neuroinvasion are not completely understood. The proinflammatory chemokine osteopontin (OPN) is induced in multiple neuroinflammatory diseases and is responsible for leukocyte recruitment to sites of its expression. In this study, we found that WNV infection induced OPN expression in both human and mouse cells. Interestingly, WNV-infected OPN deficient (Opn−/−) mice exhibited a higher survival rate (70%) than wild type (WT) control mice (30%), suggesting OPN plays a …

Engaging Narratives Evoke Similar Neural Activity And Lead To Similar Time Perception, Samantha S. Cohen, Simon Henin, Lucas C. Parra

Publications and Research

It is said that we lose track of time - that “time flies” - when we are engrossed in a story. How does engagement with the story cause this distorted perception of time, and what are its neural correlates? People commit both time and attentional resources to an engaging stimulus. For narrative videos, attentional engagement can be represented as the level of similarity between the electroencephalographic responses of different viewers. Here we show that this measure of neural engagement predicted the duration of time that viewers were willing to commit to narrative videos. Contrary to popular wisdom, engagement did not …

Normal Behavioral Responses To Light And Darkness And The Pupillary Light Reflex Are Dependent Upon The Olivary Pretectal Nucleus In The Diurnal Nile Grass Rat, Andrew J. Gall, Ohanes S. Khacherian, Brandi Ledbetter, Sean P. Deats, Megan Luck, Laura Smale, Lily Yan, Antonio A. Nunez

Faculty Publications

The olivary pretectal nucleus (OPT) is a midbrain structure that receives reciprocal bilateral retinal projections, is involved in the pupillary light reflex, and connects reciprocally with the intergeniculate leaflet (IGL), a retinorecipient brain region that mediates behavioral responses to light pulses (i.e., masking) in diurnal Nile grass rats. Here, we lesioned the OPT and evaluated behavioral responses in grass rats to various lighting conditions, as well as their anxiety-like responses to light exposure. While control grass rats remained diurnal, grass rats with OPT lesions exhibited a more night-active pattern under 12h:12h light-dark (LD) conditions. However, when placed in constant darkness, …

Girk2 And Gababr1 Downregulate In Response To Ttx As Girk2, Gababr1, And Gababr2 Are Not Affected By Bc Treatment, Staci E. Hammer, Amanda Weiss, Hee Jung Chung

PRECS student projects

Homeostatic plasticity is the response neurons undergo to regulate changes in excitability levels and bring the cells back to homeostasis. Research on homeostatic plasticity at the molecular level can lead to improved treatments for neurological diseases such as epilepsy, Alzheimer's, and schizophrenia. The research featured in this poster looks at the response of GIRK (G protein-gated inwardly rectifying potassium) channels and GABAb (gamma-amniobutyric acid) receptors to neurotoxins, tetrodotoxin (TTX) or bicuculline (BC).

Prolonged activity blockade of 48 hour TTX treatment significantly reduced GABABR1 and GIRK2 expression. This supports the idea that because these two proteins inhibit action potentials, there will …

Neuroanatomical Tracing Of The Gut -- Brain Axis, Ricardo P. Torres, Elizabeth A. Davis, Coltan G. Parker, Megan J. Dailey

PRECS student projects

This poster summarizes a variety of methods to further characterize the gut-brain axis by tracing motor and sensory nerves between the gut and brain and identifying cell bodies in the sensory ganglia. Determines the meth method to trace the sensory and motor nerves was through fluorescence and the best method to identify sensory neuron cell bodies was the Nissi stain.

Application Of Stem Cell Derived Neuronal Cells To Evaluate Neurotoxic Chemotherapy, Claudia Wing, Masaaki Komatsu, Shannon M. Delaney, Matthew Krause, Heather E. Wheeler, M. Eileen Dolan

Bioinformatics Faculty Publications

The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations …

Effects Of Language Immersion Versus Classroom Exposure On Advanced French Learners: An Erp Study, Alexandra Claire Brito

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

University students often report making significant advances in their second language (L2) ability after immersion in a nonnative language through study abroad. The degree to which late L2 learners can become nativelike in terms of L2 performance and brain processing is unclear in second language acquisition research. The link between L2 proficiency and learning context has been characterized in previous research, yet the role of learning experience in attaining nativelike brain processing of L2 remains to be elucidated. This study contrasts learners with advanced French proficiency who have attained this level with no, little, or more immersion experience through study …

Prevention Of Dendritic And Synaptic Deficits And Cognitive Impairment With A Neurotrophic Compound, Narjes Baazaoui, Khalid Iqbal

Publications and Research

Background: The use of neurotrophic factors to treat Alzheimer’s disease (AD) is hindered by their blood–brain barrier impermeability, short half-life, and severe side effects. Peptide 021 (P021) is a neurotrophic/neurogenic tetrapeptide that was derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. Admantylated glycine was added to its C-terminal to increase its blood–brain barrier permeability and decrease its degradation by exopeptidases to make it druggable. Here, we report on the preventive effect of P021 in 3 × Tg-AD, a transgenic mouse model of AD.

Methods: P021 was administered in the diet at 3 months, …

Investigating The Synergistic Effects Of Cisplatin And Two Curcuminoid Compounds On Cancer, Denis Hodzic

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an anti-cancer drug effective against several cancers which can produce the serious side-effect of hearing loss. Curcumin, a natural plant compound, can increase the activity of cisplatin against cancer and counteract cisplatin’s effect against hearing. Because curcumin exhibits poor bioavailability, there is considerable interest in developing synthetic curcumin analogs (curcuminoids) that are more soluble and which retain anti-cancer activity and otoprotective function. This study investigated whether two curcuminoids, EF-24 and CLEFMA, increase the cytotoxic and ototoxic effects of cisplatin against the lung cancer cell line, A549, and the colorectal cancer cell line, Caco2. Cytotoxicity was measured by using …

Neuroscience, Materialism, And The Soul: Limit Questions, Jeremy M. Aymard

Dialogue & Nexus

In light of recent discoveries in neuroscience linking the mind to physical processes, Christian philosophers have resorted to a more materialistic view of the human person, using neuroscience as support for their view that an immaterial soul does not exist. In this essay, I will point out a major flaw in the logic for defending a materialistic view, argue that either a bipartite or tripartite view of the human person is more aligned with Scripture, and hopefully point towards a more reliable means for attaining truth regarding human nature and the soul.

Calcineurin/Nfat Signaling In Activated Astrocytes Drives Network Hyperexcitability In AΒ-Bearing Mice, Pradoldej Sompol, Jennifer L. Furman, Melanie M. Pleiss, Susan D. Kraner, Irina A. Artiushin, Seth R. Batten, Jorge E. Quintero, Linda A. Simmerman, Tina L. Beckett, Mark A. Lovell, M. Paul Murphy, Greg A. Gerhardt, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Hyperexcitable neuronal networks are mechanistically linked to the pathologic and clinical features of Alzheimer's disease (AD). Astrocytes are a primary defense against hyperexcitability, but their functional phenotype during AD is poorly understood. Here, we found that activated astrocytes in the 5xFAD mouse model were strongly associated with proteolysis of the protein phosphatase calcineurin (CN) and the elevated expression of the CN-dependent transcription factor nuclear factor of activated T cells 4 (NFAT4). Intrahippocampal injections of adeno-associated virus vectors containing the astrocyte-specific promoter Gfa2 and the NFAT inhibitory peptide VIVIT reduced signs of glutamate-mediated hyperexcitability in 5xFAD mice, measured in vivo with …

The Motor Cortical Representation Of A Muscle Is Not Homogeneous In Brain Connectivity, Jo Armour Smith, Alaa Albishi, Sarine Babikian, Skulpan Asavasopon, Beth E. Fisher, Jason Kutch

Physical Therapy Faculty Articles and Research

Functional connectivity patterns of the motor cortical representational area of single muscles have not been extensively mapped in humans, particularly for the axial musculature. Functional connectivity may provide a neural substrate for adaptation of muscle activity in axial muscles that have both voluntary and postural functions. The purpose of this study was to combine brain stimulation and neuroimaging to both map the cortical representation of the external oblique (EO) in primary motor cortex (M1) and supplementary motor area (SMA), and to establish the resting-state functional connectivity associated with this representation. Motor evoked potentials were elicited from the EO muscle in …

Allosteric Modulatory Effects Of Sri-20041 And Sri-30827 On Cocaine And Hiv-1 Tat Protein Binding To Human Dopamine Transporter, Wei-Lun Sun, Pamela M. Quizon, Yaxia Yuan, Wei Zhang, Subramaniam Ananthan, Chang-Guo Zhan, Jun Zhu

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Dopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and Y88 F mutants. Effect of SRI-30827 on Tat-induced inhibition of [³H]WIN35,428 …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Sivasai Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Selected Works Temporary Series

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Departmental Papers (Biology)

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Igf-1 Mediated Neurogenesis Involves A Novel Rit1/Akt/Sox2 Cascade, Sajad Mir, Weikang Cai, Shaun W. Carlson, Kathryn E. Saatman, Douglas A. Andres

Molecular and Cellular Biochemistry Faculty Publications

Insulin-like growth factor 1 (IGF-1) is known to have diverse effects on brain structure and function, including the promotion of stem cell proliferation and neurogenesis in the adult dentate gyrus. However, the intracellular pathways downstream of the IGF-1 receptor that contribute to these diverse physiological actions remain relatively uncharacterized. Here, we demonstrate that the Ras-related GTPase, RIT1, plays a critical role in IGF-1-dependent neurogenesis. Studies in hippocampal neuronal precursor cells (HNPCs) demonstrate that IGF-1 stimulates a RIT1-dependent increase in Sox2 levels, resulting in pro-neural gene expression and increased cellular proliferation. In this novel cascade, RIT1 stimulates Akt-dependent phosphorylation of …

A Social Cognitive Neuroscience Approach To Information Security, Robert West, Kaitlyn Malley '19, Bridget Kirby '20, Qing Hu

Psychology and Neuroscience Faculty Publications

Information security (InfoSec) represents a significant challenge for private citizens, corporations, and government entities. Breaches of InfoSec, may lower consumer confidence (Yayla & Hu, 2011), shape national and international politics (Groll, 2017), and represent a significant threat to the world economy (e.g., estimated costs of breaches related to cybercrime were $3 trillion in 2015; Cybersecurity Ventures). Significant progress has been made in the context of developing and refining hardware and software infrastructure to thwart cybercrime (Ayuso, Gasca, & Lefevre, 2012; Choo, 2011). However, much less attention has been devoted to understanding the factors that lead individuals within an organization to …

Selective Inhibition Of Small-Diameter Axons Using Infrared Light, Emilie H. Lothet, Kendrick M. Shaw, Hui Lu, Junqi Zhuo, Yves T. Wang, Shi Gu, Hillel J. Chiel, Michael W. Jenkins

Faculty Scholarship

Novel clinical treatments to target peripheral nerves are being developed which primarily use electrical current. Recently, infrared (IR) light was shown to inhibit peripheral nerves with high spatial and temporal specificity. Here, for the first time, we demonstrate that IR can selectively and reversibly inhibit small-diameter axons at lower radiant exposures than large-diameter axons. We provide a mathematical rationale, and then demonstrate it experimentally in individual axons of identified neurons in the marine mollusk Aplysia californica, and in axons within the vagus nerve of a mammal, the musk shrew Suncus murinus. The ability to selectively, rapidly, and reversibly control small-diameter …

Disrupted Olfactory Integration In Schizophrenia: Functional Connectivity Study, Sara Kiparizoska, Toshikazu Ikuta

Faculty and Student Publications

Background

Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia.

Methods

We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory …

Between Speech & Song: Clarifying The Sprechstimme Of Schoenberg's Pierrot Lunaire, Sara M. Paar

Dissertations, Theses, and Capstone Projects

Since its creation, the technique of Sprechstimme has fascinated the audiences, performers, and composers of twentieth century music. What is it? How is it done? How should it be notated? At the fore of investigations into these questions has been Arnold Schoenberg’s Pierrot lunaire, the work in which Schoenberg debuted this new technique. Much has been written in regard to Schoenberg’s creation and use of Sprechstimme, as well as his own exploration of the speech/song continuum. Composers, conductors, and performers have all tried to make sense of the notation, instructions, and performances Schoenberg left behind. Despite this, confusion, …

Label-Free Fluorescence Spectroscopy For Detecting Key Biomolecules In Brain Tissue From A Mouse Model Of Alzheimer’S Disease, Lingyan Shi, Luyao Lu, George Harvey, Thomas Harvey, Adrián Rodríguez-Contreras, Robert R. Alfano

Publications and Research

In this study, label-free fluorescence spectroscopy was used for the first time to determine spectral profiles of tryptophan, reduced nicotinamide adenine dinucleotide (NADH), and flavin denine dinucleotide (FAD) in fresh brain samples of a mouse model of Alzheimer’s disease (AD). Our results showed that the emission spectral profile levels of tryptophan and NADH were higher in AD samples than normal samples. The intensity ratio of tryptophan to NADH and the change rate of fluorescence intensity with respect to wavelength also increased in AD brain. These results yield an optical method for detecting early stage of AD by comparing spectral profiles …

Down Syndrome: Age-Dependence Of Pib Binding In Postmortem Frontal Cortex Across The Lifespan, Harry Levine Iii, H. Peter Spielmann, Sergey V. Matveev, Francesca Macchiavello Cauvi, M. Paul Murphy, Tina L. Beckett, Katie Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh Compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro ³H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (N=25) and DS (N=39). In DS, ³H-PiB binding …