Life Sciences Commons^™

The Processing Of Amyloid Precursor Protein In The Central Nervous System Of Humans And Rhesus Macaques, Justyna Anna Dobrowolska

All Theses and Dissertations (ETDs)

Alzheimer's disease: AD) is the most common dementia, currently afflicting 30 million people worldwide, with prevalence steadily increasing. Over 99% of AD cases are classified as sporadic, in which the major risk factors are age: greater than 65 years) and the ApoE-ε4 allele: in a gene dose dependent manner). The minority of AD cases: less than 1%) are caused by autosomal dominant inheritance of a genetic mutation in one of three genes: Amyloid Precursor Protein: APP), Presenilin-1: PSEN1), or Presenilin-2: PSEN2). Mutation carriers will generally notice cognitive decline starting at a relatively young age, anytime between their 30s-50s, and eventually …

The Effects Of Chronic Simvastatin Treatment On The Expression Of Behavioral Symptoms In A Transgenic Mouse Model Of Huntington’S Disease, Ashley Whitmarsh

University of New Orleans Theses and Dissertations

Huntington’s disease (HD) is a heritable, neurodegenerative disorder characterized by motor, cognitive, and psychiatric disturbances. An unstable CAG expansion within the gene normally encoding for the Huntingtin protein is responsible. The expanded mutant form of Huntingtin and the putative protein co-factor Rhes interact and cause cell death within the striatum. We hypothesized chronic treatment with simvastatin, a cholesterol lowering drug, would disrupt the biosynthetical pathway which gives both Rhes and its target cells binding sites and render Rhes inactive. Healthy and HD mice were treated with simvastatin or a vehicle. Animals’ motor behavior was assessed with three separate tests over …

Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott

Dartmouth Scholarship

Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group …

The Hippocampus Participates In A Pharmacological Rat Model Of Absence Seizures, Justin Andrew Arcaro

Electronic Thesis and Dissertation Repository

The thalamocortical network is responsible for the generation of spike-and-wave discharges (SWDs) in absence epilepsy. Recent studies suggest a potential involvement of the hippocampus, which may explain the variability in the extent of cognitive deficits among patients with absence epilepsy. I hypothesize that the hippocampus may become entrained in spike-and-wave discharges following thalamocortical activation. The gamma-butyrolactone (GBL) rat model of absence seizures was used in this thesis. Following GBL injection, SWDs of 4 to 6 Hz developed in the spontaneous local field potentials (LFPs) recorded by depth electrodes in the thalamus, neocortex and hippocampus. Synchronization of hippocampal, thalamic and neocortical …

Reaching For The Light: The Prioritization Of Conspicuous Visual Stimuli For Reflexive Target-Directed Reaching, Daniel K. Wood

Electronic Thesis and Dissertation Repository

The degree to which something stands out against the background of its environment communicates important information. The phenomenon of camouflage is a testament of the degree to which visual salience and probability of survival tend to overlap. Salient stimuli often elicit fast, reflexive movements in order to catch prey or avoid a predator. The overarching goal of the work presented in this thesis is to investigate how the physical salience of visual stimuli influence the programming and execution of reaching movements. I approached this question by recording kinematics and muscle responses during reaching movements. Broadly, this thesis investigates the effect …

Field Effects And Ictal Synchronization: Insights From In Homine Observations, Shennan A. Weiss, Guy Mckhann Jr., Robert Goodman, Ronald G. Emerson, Andrew Trevelyan, Marom Bikson, Catherine A. Schevon

Publications and Research

It has been well established in animal models that electrical fields generated during inter-ictal and ictal discharges are strong enough in intensity to influence action potential firing threshold and synchronization. We discuss recently published data from microelectrode array recordings of human neocortical seizures and speculate about the possible role of field effects in neuronal synchronization. We have identified two distinct seizure territories that cannot be easily distinguished by traditional EEG analysis. The ictal core exhibits synchronized neuronal burst firing, while the surrounding ictal penumbra exhibits asynchronous and relatively sparse neuronal activity. In the ictal core large amplitude rhythmic ictal discharges …

Contribution Of Trpm2 To Memory Loss In An Alzheimer's Mouse Model, Megan M. Chen

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive deterioration of memory and other intellectual abilities. Accumulation of amyloid-β (Aβ) peptide, the major contributor to the senile plaques central to AD, is thought to mediate neurotoxicity by inducing oxidative stress and calcium dysregulation. Transient Receptor Potential Melastatin type 2 (TRPM2) is a calcium permeable, non-selective cation channel activated under oxidative stress and ultimately induces cell death. The APPSWE/PSEN1ΔE9 double transgenic mouse model carries the human APPswe (Swedish mutations K594N/M595L) and PS1 mutations with a deletion in exon 9 (PS1-dE9), and is one of the most commonly used AD …

Acceleration Of Image Analyst Training With Transcranial Direct Current Stimulation, R. Andy Mckinley, Lindsey Mcintire, Nathaniel Bridges, Charles Goodyear, Michael Patrick Weisend

Wright State Research Institute Publications

Humans today are routinely and increasingly presented with vast quantities of data that challenge their capacity for efficient processing. To restore the balance between man and machine, it is worthwhile to explore new methods for enhancing or accelerating this capacity. This study was designed to investigate the efficacy of transcranial DC stimulation (tDCS) to reduce training time and increase proficiency in spatial recognition using a simulated synthetic aperture radar (SAR) task. Twenty-seven Air Force active duty members volunteered to participate in the study. Each participant was assigned to 1 of 3 stimulation groups and received two, 90-min training sessions on …

Neural Responses During Trace Conditioning With Face And Non-Face Stimuli Recorded With Magnetoencephalography, Nicholas Lee Balderston

Theses and Dissertations

During fear conditioning a subject is presented with an initially innocuous stimulus like an image (conditioned stimulus; CS) that predicts an aversive outcome like a mild electric shock (unconditioned stimulus; UCS). Subjects rapidly learn that the CS predicts the UCS, and show autonomic fear responses (CRs) during the presentation of the CS. When the CS and the UCS coterminate, as is the case for delay conditioning, individuals can acquire CRs even if they are unable to predict the occurrence of the UCS. However when there is a temporal gap between the CS and the UCS, CR expression is typically dependent …

Automated Annotation Of Functional Imaging Experiments Via Multi-Label Classification, Matthew Turner, Chayan Chakrabarti, Thomas B. Jones, Jiawei F. Xu, Peter T. Fox, George F. Luger, Angela R. Laird, Jessica A. Turner

Neuroscience Institute Faculty Publications

Identifying the experimental methods in human neuroimaging papers is important for grouping meaningfully similar experiments for meta-analyses. Currently, this can only be done by human readers. We present the performance of common machine learning (text mining) methods applied to the problem of automatically classifying or labeling this literature. Labeling terms are from the Cognitive Paradigm Ontology (CogPO), the text corpora are abstracts of published functional neuroimaging papers, and the methods use the performance of a human expert as training data. We aim to replicate the expert’s annotation of multiple labels per abstract identifying the experimental stimuli, cognitive paradigms, response types, …

The Role Of The Amygdala, Retrosplenial Cortex, And Medial Prefrontal Cortex In Trace Fear Extinction And Reconsolidation, Janine Lynn Kwapis

Theses and Dissertations

A wealth of research has outlined the neural circuits responsible for the consolidation, reconsolidation, and extinction of standard "delay" fear conditioning, in which awareness is not required for learning. Far less is understood about the neural circuit supporting more complex, explicit associations. "Trace" fear conditioning is considered to be a rodent model of explicit fear because it relies on the cortex and hippocampus and requires explicit contingency awareness in humans for successful acquisition. In the current set of studies, we aimed to better characterize the neural circuit supporting the consolidation, reconsolidation, and extinction of trace fear in order to better …

Distinct Phenotypes In Zebrafish Models Of Human Startle Disease, Lisa R. Ganser, Qing Yan, Victoria M. James, Robert Kozol, Maya Topf, Robert J. Harvey, Julia E. Dallman

Faculty and Research Publications

Startle disease is an inherited neurological disorder that causes affected individuals to suffer noise- or touch-induced non-epileptic seizures, excessive muscle stiffness and neonatal apnea episodes. Mutations known to cause startle disease have been identified in glycine receptor subunit (GLRA1 and GLRB) and glycine transporter (SLC6A5) genes, which serve essential functions at glycinergic synapses. Despite the significant successes in identifying startle disease mutations, many idiopathic cases remain unresolved. Exome sequencing in these individuals will identify new candidate genes. To validate these candidate disease genes, zebrafish is an ideal choice due to rapid knockdown strategies, accessible embryonic stages, and stereotyped behaviors. The …

Iptakalim Attenuates Self-Administration And Acquired Goal-Tracking Behavior Controlled By Nicotine, S. Charntikov, N. Swalve, Steven T. Pittenger, K. Fink, S. Schepers, G. C. Hadlock, A. E. Fleckenstein, G. Hu, Ming Li, Rick A. Bevins

Department of Psychology: Faculty Publications

Iptakalim is an ATP-sensitive potassium channel opener, as well as an a4b2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0.4 mg/kg, SC) and saline sessions. Sucrose was intermittently presented in a responseindependent manner only on nicotine sessions. …

Repeated Asenapine Treatment Produces A Sensitization Effect In Two Preclinical Tests Of Antipsychotic Activity, Rongyin Qin, Yingzhu Chen, Ming Li

Department of Psychology: Faculty Publications

Among several commonly used atypical antipsychotic drugs, olanzapine and risperidone cause a sensitization effect in the conditioned avoidance response (CAR) and phencyclidine (PCP)- induced hyperlocomotion paradigms – two well established animal tests of antipsychotic drugs, whereas clozapine causes a tolerance effect. Asenapine is a novel antipsychotic drug recently approved for the treatment of schizophrenia and manic disorders. It shares several receptor binding sites and behavioral features with other atypical antipsychotic drugs. However, it is not clear what type of repeated effect (sensitization or tolerance) asenapine would induce, and whether such an effect is transferrable to other atypicals. In this study, …

The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki

Theses and Dissertations

Developing neurons extend processes to specific targets and establish connections that are essential for future function of the nervous system. One of these processes, the axon, has a motile tip called a growth cone that rearranges its membrane-associated actin cytoskeleton to turn toward or away from environmental guidance cues. Growth associated protein 43 (GAP-43) is one of the most abundant proteins associated with axonal growth cone membranes and is known to modulate the formation and stability of the actin cytoskeleton during axon guidance. Protein kinase C (PKC)-mediated phosphorylation of GAP-43 on serine 42 regulates its interactions with actin. Phosphorylated GAP-43 …

Mtorc1 Signaling In Memory Formation And Dysfunction, Natalia S. Rozas De O'Laughlin

Dissertations & Theses (Open Access)

The mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway integrates cellular availability of growth factors, energy and amino acids to regulate protein synthesis and autophagy. The mTORC1 pathway has also been shown to be required for memory consolidation, and its dysregulation is associated with many neurological disorders. MTORC1 is negatively regulated by the tuberous sclerosis complex (TSC1/2). When ATP and growth factors are available, TSC1/2 is inhibited and mTORC1 activity can be restored. In a complementary regulatory pathway, amino acids signal to mTORC1 through the Rag GTPases and Ragulator complex, which modulate the translocation of mTORC1 from the cytoplasm to …

Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum

Dissertations & Theses (Open Access)

Understanding speech in face-to-face conversation utilizes the integration of multiple pieces of information, most importantly the auditory vocal sounds and visual lip movements. Prior studies of the neural underpinnings of audiovisual integration in the brain have provided converging evidence to suggest that neurons within the left superior temporal sulcus (STS) provide a critical neural hub for the integration of auditory and visual information in speech. While most studies of audiovisual processing focus on neural mechanisms within healthy, young adults, we currently know very little about how changes to the brain can affect audiovisual integration in speech. To examine this further, …

The Development Of A Traumatic Brain Injury Bioreactor, Zachery Heller

Graduate Theses and Dissertations

Approximately 1.7 million Americans experience a traumatic brain injury (TBI) each year. Concussive injuries are a subset of TBI in which blows to the head cause the brain to collide against the interior of the skull. Damage to the neurons, supporting cells, and surrounding extra cellular matrix resulting from these collisions can lead to permanent physical, cognitive, and psychological impairment. We believe the prevalence and clinical significance of concussive injures warrants research investment. To study brain injury following TBI, in vivo models have been the gold standard for TBI experiments. Although a valuable research alternative, animals are expensive, raise ethical …

Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz

Dissertations & Theses (Open Access)

Plakophilin-3, the less studied member of the plakophilin-catenin subfamily, and the larger catenin family, binds directly to desmosomal cadherin cytoplasmic domains and enhances desmosome formation and stability. In mammals, plakophilin-3 is expressed at the highest levels in desmosome-enriched tissues such as epithelia, with the knock-out in mice producing corresponding reductions in ectodermal integrity. In tissue, cellular and intracellular contexts where plakophilin-3 is not at the desmosomal plaque, little is known about its functions in the cytoplasm or nucleus, where it also localizes.

My work employed embryos of the amphibian, Xenopus laevis, to examine plakophilin-3’s developmental roles. I first evaluated …

On The Evolution Of The Serotonin Transporter Linked Polymorphic Region (5-Httlpr) In Primates, Seth D. Dobson, Lauren J.N Brent

Dartmouth Scholarship

Some allelic variants of the serotonin transporter linked polymorphic region (5-HTTLPR) result in lower levels of expression of the serotonin transporter gene (SLC6A4). These low-expressing (LE) alleles are associated with mental-health disorders in a minority of humans that carry them. Humans are not the only primates that exhibit this polymorphism; other species, including some monkeys, also have LE and high-expressing (HE) variants of 5-HTTLPR. We propose a behavioral genetic framework to explain the adaptive evolution of this polymorphism in primates, including humans. We hypothesize that both LE and HE alleles are maintained by balancing selection in species characterized …

Short Duration Waveforms Recorded Extracellularly From Freely Moving Rats Are Representative Of Axonal Activity, Ashlee A. Robbins, Steven E. Fox, Gregory L. Holmes, Rod C. Scott, Jeremy M. Barry

Dartmouth Scholarship

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation …

Socially Excluded Individuals Fail To Recruit Medial Prefrontal Cortex For Negative Social Scenes, Katherine E. Powers, Dylan D. Wagner, Catherine J. Norris, Todd F. Heatherton

Dartmouth Scholarship

Converging behavioral evidence suggests that people respond to experiences of social exclusion with both defensive and affiliative strategies, allowing them to avoid further distress while also encouraging re-establishment of positive social connections. However, there are unresolved questions regarding the cognitive mechanisms underlying people's responses to social exclusion. Here, we sought to gain insight into these behavioral tendencies by using functional magnetic resonance imaging (fMRI) to examine the impact of social exclusion on neural responses to visual scenes that varied on dimensions of sociality and emotional valence. Compared to socially included participants, socially excluded participants failed to recruit dorsomedial prefrontal cortex …

A Novel Signal Processing Method For Intraoperative Neurophysiological Monitoring In Spinal Surgeries, Krishnatej Vedala

FIU Electronic Theses and Dissertations

Intraoperative neurophysiologic monitoring is an integral part of spinal surgeries and involves the recording of somatosensory evoked potentials (SSEP). However, clinical application of IONM still requires anywhere between 200 to 2000 trials to obtain an SSEP signal, which is excessive and introduces a significant delay during surgery to detect a possible neurological damage. The aim of this study is to develop a means to obtain the SSEP using a much less, twelve number of recordings. The preliminary step involved was to distinguish the SSEP with the ongoing brain activity. We first establish that the brain activity is indeed quasi-stationary whereas …

Metergoline, The Basolateral Amygdala And The Ventral Pallidum: Implications For Panic Disorder, Douglas Ryan Schuweiler

Theses and Dissertations

Panic disorder (PD) is a common mental illness characterized by recurring spontaneous panic attacks. Scientific investigation into PD has been accelerated by the development of rat models of PD. These models can be validated by responses to intravenous sodium lactate (NaLac), including tachycardia, that are similar to PD patient responses. Previous work on established PD models has suggested that antagonism of serotonin (5-HT) receptors in the basolateral amygdala (BLA) may be sufficient to model PD. To test this hypothesis metergoline (MET), a 5-HT receptor antagonist, or vehicle was microinjected into the BLA of anesthetized rats. Following the microinjection, NaLac or …

Progressive Levels Of Physical Dependence To Tobacco Coincide With Changes In The Anterior Cingulum Bundle Microstructure, Wei Huang, Joseph R. Difranza, David N. Kennedy, Nanyin Zhang, Douglas M. Ziedonis, W. W. Sanouri A. Ursprung, Jean A. King

Douglas M. Ziedonis

BACKGROUND: The tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA).

METHODS: Diffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation …

Stress And Serial Adult Metamorphosis: Multiple Roles For The Stress Axis In Socially Regulated Sex Change, Tessa Solomon-Lane, Erica J. Crespi, Matthew S. Grober

Neuroscience Institute Faculty Publications

Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses …

Spatial Warping By Oriented Line Detectors Can Counteract Neural Delays, Don A. Vaughn, David M. Eagleman

Faculty Publications

The slow speed of neural transmission necessitates that cortical visual information from dynamic scenes will lag reality. The "perceiving the present" (PTP) hypothesis suggests that the visual system can mitigate the effect of such delays by spatially warping scenes to look as they will in ~100 ms from now (Changizi, 2001). We here show that the Hering illusion, in which straight lines appear bowed, can be induced by a background of optic flow, consistent with the PTP hypothesis. However, importantly, the bowing direction is the same whether the flow is inward or outward. This suggests that if the warping is …

Moral Dilemma Judgment Revisited: A Loreta Analysis, Armando F. Rocha, Fábiot T. Rocha, Eduardo Massad

Armando F Rocha

Recent neuroscience investigations on moral judgment have provided useful information about how brain processes such complex decision making. All these studies so were fMRI investigations and therefore constrained by the poor resolution of this technique. Recent advances in electroencephalography (EEG) analysis provided by Low Resolution Tomogray (Loreta), Principal Component (PCA), Correlation and Regression Analysis improved EEG spatial resolution and make EEG a very useful technique in decision-making studies. Here, we reinvestigate previously fMRI study of personal (PD) and impersonal (ID) moral dilemma judgment, taking profit of these new EEG analysis improvements. Compared to the previous fMRI results, Loreta and PCA …

Cultural Perceptions Of Traumatic Brain Injury And Rehabilitation In Minorities, Lyanna Díaz

Sound Neuroscience: An Undergraduate Neuroscience Journal

A person's culture can greatly affect the way they perceive illnesses, doctor-patient interactions, and rehabilitation. Factors include family, religion, and values. A lack of cultural competency training in the health professions may be detrimental to the recovery process of minorities. This phenomenon is examined in depth as it relates to Traumatic Brain Injury (TBI).

The Treatment Of Mental Disorders Through Medication, Jessica Jaynes

Sound Neuroscience: An Undergraduate Neuroscience Journal

Diagnosis plays a huge role in the successful treatment of mental disorders. Subtle differences in symptoms can lead to different diagnoses, and therefore different prescribed medications. The neurological causes of anxiety, depression, bipolar disorder, and ADHD are examined; as well as the mechanisms of the drugs commonly used to treat them.