Neuroscience and Neurobiology 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

LSU 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 …

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 …

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 …

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, …

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. …

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 Articles

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 …

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

Dissertations and 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 …

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

Dissertations and 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 and 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 …

Neuroscience, Memory And Art: Deborah Aschheim, Sara Gevurtz

SWITCH

This article recounts a discussion with artist Deborah Aschheim and explores the intersections of neuroscience, memory, and art. Aschheim’s work investigates memory, memory loss, and place through interactive sculptures and installations, often incorporating sound and collaboration with musicians and scientists.

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 …

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 …

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

Faculty, Staff and Students 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 …

Analysis Of Neuronal And Microglial Responses To Implanted Silicon Devices Through Immunohistochemistry And Clarity, Michael A. Leathers, Kevin J. Otto

The Summer Undergraduate Research Fellowship (SURF) Symposium

Brain computer interfaces (BCI’s) and implantable cortical devices have recently emerged in research as promising treatment methods for a variety of neurological problems such as motor dysfunction, memory loss, and sudden onset seizures. The number of people currently suffering from a loss of nervous system function as a result of neurodegenerative diseases or injury creates a need for reliable neural prostheses. The autoimmune response of the Central Nervous System (CNS) when introduced with a foreign object such as an electrode shank quickly impedes signal strength and degrades the functional life of the device. Two different experimental methods were used to …

Social Compass Curriculum: Three Descriptive Case Studies Of Social Skills Outcomes For Students With Autism, Louanne E. Boyd, Deborah M. Ward

Engineering Faculty Articles and Research

The Social Compass Curriculum (SCC) was investigated for its effectiveness in improving core social skills in three descriptive case studies of students with autism. Treatment fidelity of the SCC was also measured in the school setting. The Social Responsiveness Scale and the Autism Social Skills Profile were completed by parents to measure pre- and postintervention social skills for three students aged 8 to 11 years who participated in the present multisite pilot study. Fidelity of implementation data were collected via a checklist during observations for three educators who implemented the intervention. Results indicate that the SCC improved core social deficits …

An Investigation Into The Presynaptic Actions By Which Amphetamine Activates Dopamine Signaling Within Striatal Subregions Of The Rat., Dan P. Covey

Theses and Dissertations

Despite decades of intense research and a consensus view in the field, the work presented herein provides strong evidence that the primary mechanism of amphetamine action should be re-evaluated. Rather than depleting vesicular dopamine stores and promoting non-exocytotic efflux through the dopamine transporter in vivo, recent evidence demonstrates that amphetamine augments phasic dopamine signaling instead. This signaling modality is critical for reinforcement learning and is dependent on intact vesicular stores. The new findings support over-activation of phasic dopamine signaling as a common mechanism in the addiction process.

Day-Night Differences In Neural Activation In Histaminergic And Serotonergic Areas With Putative Projections To The Cerebrospinal Fluid In A Diurnal Brain, Alexandra Castillo-Ruiz, Andrew J. Gall, Laura Smale, Antonio A. Nunez

Faculty Publications

In nocturnal rodents, brain areas that promote wakefulness have a circadian pattern of neural activation that mirrors the sleep/wake cycle, with more neural activation during the active phase than during the rest phase. To investigate whether differences in temporal patterns of neural activity in wake-promoting regions contribute to differences in daily patterns of wakefulness between nocturnal and diurnal species, we assessed Fos expression patterns in the tuberomammillary (TMM), supramammillary (SUM), and raphe nuclei of male grass rats maintained in a 12:12 h light-dark cycle. Day-night profiles of Fos expression were observed in the ventral and dorsal TMM, in the SUM, …

Sex Differences In White Matter Development During Adolescence: A Dti Study, Yingying Wang, Chris Adamson, Weihong Yuan, Mekibib Altaye, Anna W. Byars, Scott K. Holland

Center for Brain, Biology, and Behavior: Faculty Publications

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity …

Cervicothoracic Multisegmental Transpinal Evoked Potentials In Humans, Jonathan Einhorn, Alan Li, Royi Hazan, Maria Knikou

Publications and Research

The objectives of this study were to establish the neurophysiological properties of the transpinal evoked potentials (TEPs) following transcutaneous electric stimulation of the spine (tsESS) over the cervicothoracic region, changes in the amplitude of the TEPs preceded by median nerve stimulation at group I threshold, and the effects of tsESS on the flexor carpi radialis (FCR) H-reflex in thirteen healthy human subjects while seated. Two re-usable self-adhering electrodes, connected to function as one electrode (cathode), were placed bilaterally on the clavicles. A re-usable electrode (anode) was placed on the cervicothoracic region covering from Cervical 4 – Thoracic 2 and held …

Combined Erp/Fmri Evidence For Early Word Recognition Effects In The Posterior Inferior Temporal Gyrus, Joseph Dien, Eric S. Brian, Dennis L. Molfese, Brian T. Gold

Center for Brain, Biology, and Behavior: Faculty Publications

Two brain regions with established roles in reading are the posterior middle temporal gyrus and the posterior fusiform gyrus. Lesion studies have also suggested that the region located between them, the posterior inferior temporal gyrus (pITG), plays a central role in word recognition. However, these lesion results could reflect disconnection effects since neuroimaging studies have not reported consistent lexicality effects in pITG. Here we tested whether these reported pITG lesion effects are due to disconnection effects or not using parallel ERP/fMRI studies. We predicted that the Recognition Potential (RP), a left-lateralized ERP negativity that peaks at about 200–250 ms, might …

Reasoning Across Language And Vision In Machines And Humans, Andrei Barbu

Open Access Dissertations

Humans not only outperform AI and computer-vision systems, but use an unknown computational mechanism to perform tasks for which no suitable approaches exist. I present work investigating both novel tasks and how humans approach them in the context of computer vision and linguistics. I demonstrate a system which, like children, acquires high-level linguistic knowledge about the world. Robots learn to play physically-instantiated board games and use that knowledge to engage in physical play. To further integrate language and vision I develop an approach which produces rich sentential descriptions of events depicted in videos. I then show how to simultaneously detect …

Network Structure And Dynamics Of The Mental Workspace, Alexander Schlegel, Peter J. Kohler, Sergei V. Fogelson, Prescott Alexander

Dartmouth Scholarship

The conscious manipulation of mental representations is central to many creative and uniquely human abilities. How does the human brain mediate such flexible mental operations? Here, multivariate pattern analysis of functional MRI data reveals a widespread neural network that performs specific mental manipulations on the contents of visual imagery. Evolving patterns of neural activity within this mental workspace track the sequence of informational transformations carried out by these manipulations. The network switches between distinct connectivity profiles as representations are maintained or manipulated.

Effects Of Dip-Coated Films On The Properties Of Implantable Intracortical Microelectrodes, Salah Sommakia

Open Access Dissertations

The successful clinical use of implantable intracortical microelectrodes (ICMs) to treat certain types of deafness, blindness, and paralysis is limited by a reactive tissue response (RTR) of the brain. This RTR culminates in the formation of a tight glial scar and a loss of neuronal density around implanted ICMs, and is accompanied by a decrease in signal to noise ratio and an increase in impedance. While no comprehensive mechanistic understanding of the underlying biology is currently agreed upon in the field, a general consensus exists around a highly volatile acute RTR phase. During this acute phase, the electrical properties of …

Smooth Muscle-Specific Removal Of Brain-Derived Neurotrophic Factor Results In Increased Vagal Afferent Innervation To The Intestine And Increased Satiation In Mice, Jessica Erin Biddinger

Open Access Dissertations

Vagal afferents transmit signals regarding food-derived stimuli in the gastrointestinal (GI) tract to the brain. Vagal mechanoreceptors called intraganglionic laminar endings (IGLEs) innervate the smooth muscle wall of GI organs and detect stretch and tension to regulate GI reflexes and satiation. Brain-derived neurotrophic factor (BDNF) is expressed in the smooth muscle of developing GI organs when vagal afferents from the nodose ganglion begin to innervate the GI tract. Therefore, it was hypothesized BDNF is necessary for development of vagal afferents that innervate this tissue. Targeted smooth muscle-specific BDNF homozygous knockout (BDNF SM -/-) mice were generated and .vagal afferent innervation …

Effects Of Hearing Aid Amplification On Robust Neural Coding Of Speech, Jonathan Daniel Boley

Open Access Dissertations

Hearing aids are able to restore some hearing abilities for people with auditory impairments, but background noise remains a significant problem. Unfortunately, we know very little about how speech is encoded in the auditory system, particularly in impaired systems with prosthetic amplifiers. There is growing evidence that relative timing in the neural signals (known as spatiotemporal coding) is important for speech perception, but there is little research that relates spatiotemporal coding and hearing aid amplification.

This research uses a combination of computational modeling and physiological experiments to characterize how hearing aids affect vowel coding in noise at the level of …