Neuroscience and Neurobiology Commons^™

Brain Mechanism For Enhanced Hand Function With Remote Sensory Stimulation, Kishor Lakshminarayanan

Theses and Dissertations

The neurological bases for remote vibration enhanced sensory feedback and motor function are yet poorly understood. The purpose of this dissertation was to identify and examine the effect of vibration on finger tactile sensation in healthy adults and how imperceptible random vibration applied to the wrist changes cortical activity for fingertip sensation and precision grip. In a series of studies on healthy adults, white-noise vibration was applied to one of four locations (dorsum hand by the second knuckle, thenar and hypothenar areas, and volar wrist) at one of four intensities (zero, 60%, 80%, and 120% of the sensory threshold for …

Investigation Of Neural Mechanisms Of Grip Relaxation, Binal Motawar

Theses and Dissertations

Neural mechanisms for grip relaxation are relatively unknown and understudied, as compared to mechanisms for grip initiation. Yet, termination of motor activity is as important as initiation in daily function. This knowledge gap presents incomplete understanding of neural control of hand function and its impairment with aging and neurologic disorders. The purpose of this dissertation was to identify and examine neural mechanisms of grip relaxation in healthy young adults, with aging, and in chronic stroke survivors. A series of experiments in healthy young adults showed that the relaxation from a maximum power grip was mediated by increase in the short-interval …

Eye Movement Effects In Simulated Object Recognition Memory Impairment, Dmitriy Kazakov

Theses and Dissertations

Malingering is the purposeful fabrication of symptoms for secondary gain. Memory problems are the most reported symptom, and object recognition tests are often used in clinical settings to evaluate these claims. Past research has shown that eye movements can indirectly index memory, in that greater viewing is directed at studied stimuli 500-750 ms after display onset. The present study evaluated eye movements as a potential method of detecting feigned memory impairment. Forty-eight participants, half simulators, studied standardized images and took a memory test. Several levels of analysis were used to detect broad trends and brief effects. Simulators performed significantly worse …

Cannabis Use And Affective Processing: A Brain Structure Analysis, Kristin E. Maple

Theses and Dissertations

Cannabis is the most commonly used illicit drug amongst adolescents and young adults in the United States. Previously, cannabis and its components have been associated with differences in affective processing and neural functioning. Participants (ages 16-25) were cannabis users and non-users excluded for psychiatric disorders, major medical conditions, and excessive other drug use. A series of multiple regressions examined whether past year cannabis use and cannabis x gender predicted measures of emotional face processing (using the PennCNP affective battery) as well as volumes in bilateral prefrontal, temporal, limbic, and cerebellar regions, as well as frontolimbic white matter tracts. Subsequently, Pearson …

Gap Junction Communication In Memory Retrieval And Extinction Of Cocaine Seeking, Michael Fitzgerald

Theses and Dissertations

Blocking drug-associated memory retrieval or enhancing extinction of drug-seeking behavior are two strategies that could limit relapse in drug addicts. The loci of retrieval and extinction memory processes include the prelimbic medial prefrontal cortex and the infralimbic medial prefrontal cortex, respectively. The neurochemical and synaptic mechanisms underlying drug-related behavior have received considerable attention, but extrasynaptic mechanisms are relatively unexplored. One form of cellular communication, gap junction communication, may play a role in drug-related learning and memory. Gap junction communication between neurons and astrocytes provide a cytoplasmic continuity between connected cells and both neuronal and astrocytic gap junction communication have been …

Foot Kinematics And Neuromuscular Preactivation In Habitual Forefoot And Rearfoot Runners, Rhiannon Seneli

Theses and Dissertations

As the rate of running related injuries has failed to decline despite advances in footwear, many researchers have begun focusing on different foot strike patterns possible contribution to injury risk. While many studies have focused on the differences between RFS and FFS running, few have investigated kinematic differences within the distal foot in habitual RFS and FFS runners and have failed to consider mechanical and neuromuscular changes due to fatigue. The purpose of this study, therefore, was to investigate foot kinematics and neuromuscular differences between RFS and FFS runners at the beginning and end of an exhaustive run. Fifteen habitual …

Functionally Distinct Pools Of Calcineurin Contribute To Depotentiation-Like Synaptic Changes In The Lateral Amygdala During Auditory Fear Extinction, Elena Kay Rotondo

Theses and Dissertations

Until recently, auditory fear extinction was not thought to modify substrates involved in the storage of the original auditory fear memory. Evidence now suggests that extinction results in the reversal of the fear conditioning-induced potentiation of thalamic inputs to the lateral amygdala. However, little is known about the molecular mechanisms that support this depotentiation of synaptic strength. Here we present behavioral and molecular evidence in support of the contribution of two distinct pools of the protein phosphatase calcineurin to depotentiation-like changes in lateral amygdala AMPA receptor trafficking during auditory fear extinction. Calcineurin protein that exists prior to the onset of …

Neural Mechanisms Supporting Differential Auditory Fear Conditioning, Nicole Christine Ferrara

Theses and Dissertations

Pavlovian fear conditioning provides an ideal way to study memory formation, retention, and updating. Plasticity in the auditory thalamus is required during the acquisition and consolidation of a fear memory when a tone signals a foot shock. The medial geniculate nucleus (MgN) of the auditory thalamus sends projections to the amygdala and auditory cortex and is functionally divided into two different regions, the medial division (MGm) and the ventral division (MGv). Traditionally, these divisions are thought to relay auditory information to the amygdala during fear-related associative learning. However, recent research has suggested a more complex role for the MgN when …

Effects Of Global Dna Methylation Changes On Neurobehavior In Zebrafish, Matthew Christopher Pickens

Theses and Dissertations

A number of environmental neurotoxicants modulate DNA methylation, but its influence on neurobehavior remains unclear. The laboratory has established that low-level developmental methylmercury exposure induces neurobehavioral deficits; the current results demonstrate that it also induces global DNA hypomethylation. DNA methyltransferase 1-mutant zebrafish (exhibit ~70% reduction in enzymatic activity) were used to assess the role of DNA hypomethylation on behavior. Several neurobehavioral assays including the C-start escape, circadian rhythm, basic locomotion and visual-motor response (VMR) were also performed. There was a significant difference in VMR between the wild type and mutant animals. Other behavior assays revealed no significant difference, primarily due …

Relationship Between Learning-Related Synaptic And Intrinsic Plasticity Within Lateral Amygdala, Megha Sehgal

Theses and Dissertations

A central question in neuroscience is to determine the mechanisms that govern formation, storage and modulation of memories. Determining these mechanisms would allow us to facilitate new memory formation as in the case of aging-related cognitive decline or weaken preexisting pathological memories such as traumatic memories and cue-induced drug craving. Pharmacological and genetic manipulation of intrinsic neuronal excitability has been demonstrated to impact the strength of memory formation, allocation of memories, and modulation of memories through retrieval and reconsolidation-dependent processes. In addition to experimental manipulations of intrinsic excitability, intrinsic plasticity, a change in neuronal intrinsic excitability, can be brought about …

The Effects Of 830nm Light On Inflammation In Retinitis Pigmentosa, Krystal Marie Bach

Theses and Dissertations

Purpose: Retinitis Pigmentosa (RP) is an inherited retinal degenerative disease and the most common cause of blindness in developed countries, affecting approximately 1 in 4,000 people. RP is characterized by photoreceptor cell death and recent studies suggest that chronic inflammation may play a key role in the pathogenesis of RP. Currently, there are no known treatments or preventive measures to delay or halt the loss of photoreceptor cells. Photobiomodulation (PBM) by light in the far-red or near-infrared (NIR) range of the light spectrum has been documented to help promote cell survival and reduce inflammation in several disease states. Recent studies …

Regulation Of Mtor And Erk Signaling In The Amygdala Through Proteolytic Modulation Of Pp2a Activity Following Auditory Fear Learning, David Sylvan Reis

Theses and Dissertations

The consolidation of fear memories is known to depend on a number of critical cellular processes including de novo protein synthesis and 26S proteasome-dependent protein degradation following auditory fear conditioning (Jarome et al., 2011; Kwapis et al., 2011). Early work has suggested that protein degradation, mediated by the ubiquitin proteasome system (UPS), may regulate the requirement for de novo protein synthesis during memory consolidation (Jarome & Helmstetter, 2014). However, the precise way in which the UPS is able to regulate mechanisms of protein synthesis remain unclear. In the present set of experiments, we investigated the role of the protein phosphatase …

The Effects Of Antibodies In Disease Progression Of Mog-Induced Experimental Autoimmune Encephalomyelitis, Melissa Marie Riter

Theses and Dissertations

Abstract: Multiple sclerosis (MS) is an auto-inflammatory disease of the central nervous system (CNS), affecting over 400,000 people in the US. MS is primarily studied in the animal model experimental autoimmune encephalomyelitis (EAE). MS is a T cell mediated disease but there is mounting evidence for a role for B cells in MS. Previous studies have established that rMOG Induction depends on the presence of B cells, while induction using the MOG peptide covering amino acids 35-55 does not require B cells to cause disease. When plasma from the rMOG and MOG35-55 immunized WT mice was analyzed by ELISA there …

Maximizing The Effects Of Passive Training On Visuomotor Adaptation By Incorporating Other Motor Learning Strategies, Yuming Lei

Theses and Dissertations

Passive training has been shown to be an effective rehabilitation approach for stroke survivors, especially for those who suffer from severe control loss or complete paralysis. However, the effectiveness of the treatments that utilize passive assist training is still low. The goal of this dissertation was to develop a training condition that can maximize the effects of passive training on motor learning by combining its effect with other motor learning strategies. To achieve this goal, two specific aims were pursued: one aim was to determine the effects of passive training on learning a visuomotor adaptation task; and the other aim …

An Optogenetic Brain-Machine Interface For Spatiotemporal Neuromodulation, Ryan Andrew Baumgartner

Theses and Dissertations

Direct neural stimulation has recently become a standard therapy for neurological disorders such as Parkinson's Disease, Essential Tremors, and Dystonia. Currently, deep brain electro-stimulation and neuro-pharmaceutical treatments are the dominant therapeutic options available to the public. As our understanding of brain function and neurological diseases improves, we are able to develop more advanced neuromodulation techniques. These methods could become viable treatment solutions for treating brain dysfunction. Optogenetics, first introduced by a research team led by Karl Deisseroth at Stanford University, has proved to be a versatile technique with remarkable potential to be used in treatments for brain disorders, dysfunction, and …

Alcohol Use Disorders And An Fmri Stress Task: A Connectivity Analysis, Natasha E. Wright

Theses and Dissertations

Little research has been conducted on neuronal stress processing in individuals

with alcohol dependence (AD). The present study examined neural stress response in AD individuals compared to controls using an fMRI stress task, assessing amygdala

activation and its connectivity to the medial prefrontal cortex (mPFC). Further, the study

analyzed the impact of hormone levels and subjective stress on frontal-limbic

connectivity patterns.

Ten abstinent AD individuals and 11 controls were recruited. Subjects

participated in an fMRI stress task. A region of interest (amygdala) analysis was

conducted using area-under-the-curve. This activation was then examined in a whole brain functional connectivity analysis. Follow-up …

The Role Of Brain-Synthesized E2 In Hippocampal Learning And Memory Consolidation In Female Mice, Jennifer Tuscher

Theses and Dissertations

The potent estrogen 17beta-Estradiol (E2) plays a critical role in neuroprotection, serving as an important trophic factor for neurons in the hippocampus, basal forebrain, and prefrontal cortex (Brinton, 2001). In the hippocampus, E2 promotes neurogenesis (Tanapat et al., 1999, Prange-Kiel et al., 2006), protects against cell death after ischemic injury (Garcia-Segura et al., 2001, Zhao and Brinton, 2007), and helps maintain spine morphology crucial for synaptic connectivity and memory (Woolley et al., 1990; Gould et al., 1990, Woolley and McEwen, 1992, Li et al., 2004). However, the mechanisms through which E2 promotes synaptic plasticity and enhances memory function are largely …

The Hippocampus And Adult Neurogenesis: A Neural Circuit With A Common Role In Behavioral Flexibility And Detailed Memory, Brian Pochinski

Theses and Dissertations

Work with patient H.M. sparked great interest in the role of the hippocampus in learning and memory. Later, the findings that new neurons are born in the adult dentate gyrus (DG) and that they become functionally integrated in neural circuits created new excitement in the field of learning and memory. While there is ample evidence that the hippocampus and adult neurogenesis are involved in learning and memory, similar inconsistencies in both areas have clouded interpretations of their precise role. We propose that studying the role of hippocampus and neurogenesis in the DG must be merged into a more cohesive field …

Gene Regulatory Pathways Driving Central Nervous System Regeneration In Zebrafish, Ishwariya Venkatesh

Theses and Dissertations

Damage to the central nervous system (CNS) circuitry of adult mammals results in permanent disability. In contrast, the ability to regenerate damaged CNS nerves and achieve functional recovery occurs naturally in fish. The ability of fish to successfully regrow damaged CNS nerves is in part a consequence of their ability to re-express key neuronal growth-associated genes/proteins in response to CNS injury. On such protein is Growth-Associated Protein-43 (Gap43), a protein which is highly enriched in axonal growth cones during CNS development and regeneration. Experiments conducted in mammals have demonstrated that ectopic expression of GAP-43 improves axonal re-growth after injury. Using …

Neurophysiological And Morphological Plasticity In Rat Hippocampus And Medial Prefrontal Cortex Following Trace Fear Conditioning, Chenghui Song

Theses and Dissertations

Pavlovian fear conditioning provides a useful model system for investigating the mechanisms underlying associative learning. In recent years, there has been an increasing interest in "trace" fear conditioning, which requires conscious awareness of the contingency of CS and US therefore considered as a rodent model of explicit fear. Acquisition of trace fear conditioning requires an intact hippocampus and medial prefrontal cortex (mPFC), but the underlying mechanisms are still unclear. The current set of studies investigated how trace fear conditioning affects neuronal plasticity in both hippocampus and mPFC in adult rats. Trace fear conditioning significantly enhanced both intrinsic excitability and synaptic …

Memory Retrieval Is Maintained By Intrinsic And Synaptic Plasticity In Prelimbic Cortex, James Otis

Theses and Dissertations

Abnormally strong memories underlie common disorders including addiction and post-traumatic stress disorder (PTSD). Memory disruption would therefore be beneficial for treatment of these disorders. Evidence reveals that cocaine conditioned place preference (CPP) memories are susceptible to long-lasting disruption during memory retrieval. For example, inhibition of β-adrenergic receptor (β-AR) activity within the prelimbic medial prefrontal cortex (PL-mPFC) prevents cocaine CPP memory retrieval, and this retrieval impairment is both long-lasting and prevents subsequent reinstatement of the CPP. Despite this, whether PL-mPFC β-AR activity is a fundamental mechanism required to maintain retrieval of other memories is unclear. Furthermore, how PL-mPFC β-AR activity maintains …

Changes In Resting-State Functional Connectivity Following Delay And Trace Fear Conditioning Acquisition And Extinction, Douglas Hank Schultz

Theses and Dissertations

Consolidation is the process of stabilizing a recently acquired memory into a more permanent or durable form. Several studies with laboratory animals have uncovered valuable information about the process of consolidation, but less is known about the process of consolidation in healthy humans. The current study examined the consolidation of emotional memories in different brain circuits in healthy humans using resting-state fMRI. We used the acquisition and extinction of two variations of Pavlovian fear conditioning, delay and trace, which rely on slightly different circuits to examine changes in functional connectivity related to a general fear learning process and also to …

Impact Of Faah Genotype And Marijuana Use On Brain Structure And Neuropsychological Performance In Emerging Adults, Skyler Gabriel Shollenbarger

Theses and Dissertations

Introduction: Chronic MJ use may be associated with higher cognitive ability impairments (see Lisdahl et al., 2013). Regions undergoing later maturation (Gogtay 2004), may be at increased risk for MJ-induced alterations. Endogenous cannabinoid signaling (ECS) is modulated by the function the enzyme Fatty Acid Amide Hydrolase (see Ho & Hilard, 2005), thus the gene encoding for this enzyme (FAAH) impacts ECS (Sipe et al., 2002). Here, we examine the impact of MJ use and FAAH genotype on PFC complexity and underlying frontal white matter (WM) integrity in young adults. Methods: Participants included 37 MJ users and 37 non-using young adults …

Is Contextual Cue Learning Flexible? An Eye-Movement Study Of The Contextual Cueing Task, Youcai Yang

Theses and Dissertations

Visual searching can be facilitated without awareness when the target is repeatedly presented in an invariant context in tasks such as contextual cueing (Chun & Jiang 1998). A behavioral cost (increased reaction time) was observed when the target was moved to a new location but no such cost was observed when the target returned to the initial location. The lack of cost for return suggests two possible explanations: One is that the learning can update the initial learning to acquire both target locations, which suggests the implicit learning is flexible. The other is that the contextual cue leaning cannot update …

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 …

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 …

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 …

Exercise-Induced Hypoxia, Angiogenesis, And Behavioral Flexibility In The Adult Rat, Kiersten Lee Berggren

Theses and Dissertations

Exercise induces a myriad of effects on the brain from the growth of new capillaries and neurons, to improvements in cognitive performance. Additionally, recent research has shown that commencement of an exercise regimen also causes apoptosis. Therefore, it is possible that exercise-induced increases in oxygen demand cause the brain to transiently experience a state of hypoxia. To investigate this hypothesis, we measured protein levels of hypoxia inducible factor 1 alpha (HIF-1α), a transcription factor known to be upregulated in conditions of hypoxia or ischemia, in animals exposed to a single bout of treadmill exercise. After exercise animals were sacrificed at …

The Role Of A Camkii/Pka-Protein Degradation-Glur2 Pathway In The Control Of Memory Updating Following Retrieval, Timothy Jarome

Theses and Dissertations

Reconsolidation is thought to be a process whereby consolidated memories can be modified following retrieval. However, very little is known about the molecular mechanisms that regulate this reconsolidation process. In the present series of experiments we tested if memories "destabilize" or become labile following retrieval through a specific signaling pathway. We found that retrieval of a contextual fear memory differentially increased proteasome activity in the amygdala and hippocampus and resulted in unique changes in AMPA receptor subunit expression in these brain regions. These changes were dependent on CaMKII activity, which was required for increases in Rpt6-S120 phosphorylation, proteasome activity and …

Dissociation Of Β1 And Β2 Adrenergic Receptor Subtypes In Retrieval And Reconsolidation Of A Cocaine Conditioned Place Preference, Michael Fitzgerald

Theses and Dissertations

Drug-seeking behavior is maintained by encounters with drug-associated cues, and disrupting retrieval or reconsolidation of the drug-cue associations could reduce the risk of relapse. Previous work has shown beta-adrenergic receptor (beta-AR) antagonists can prevent retrieval or reconsolidation of a cocaine conditioned place preference (CPP) when administered either before or after test, respectively (Otis and Mueller, 2011; Otis et al., 2013). However, the specific beta-AR subtypes that mediate retrieval and reconsolidation of a cocaine CPP remain unknown. Here we used selective blockade of & beta-1 or beta-2-AR subtypes to determine the effects on retrieval and reconsolidation of a cocaine CPP. During …