Neuroscience and Neurobiology Commons^™

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Genes And Gene Networks Related To Age-Associated Learning Impairments, Raihan Uddin

Electronic Thesis and Dissertation Repository

The incidence of cognitive impairments, including age-associated spatial learning impairment (ASLI), has risen dramatically in past decades due to increasing human longevity. To better understand the genes and gene networks involved in ASLI, data from a number of past gene expression microarray studies in rats are integrated and used to perform a meta- and network analysis. Results from the data selection and preprocessing steps show that for effective downstream analysis to take place both batch effects and outlier samples must be properly removed. The meta-analysis undertaken in this research has identified significant differentially expressed genes across both age and ASLI …

Exploring And Training Spatial Reasoning Via Eye Movements: Implications On Performance, Victoria A. Roach

Electronic Thesis and Dissertation Repository

This dissertation sought to determine if eye movements could serve as an indicator of success in spatial reasoning, and if eye movements associated with successful completion could be applied to strategically improve spatial reasoning.

Using the line images of Shepard and Metzler, an electronic test of mental rotations ability (EMRT) was designed. Two versions of the test were created, allowing for both a timed (6 seconds per question) and untimed testing environment. Four experiments were designed and completed to relate mental rotation ability (MRA) scores from the EMRT, to patterns in chrononumeric and visual salience data. In each experiment, participants …

Seasonality Of The Stress Response In House Sparrows (Passer Domesticus)., Michael R. Hasstedt

Electronic Thesis and Dissertation Repository

Seasonal changes in plasma corticosterone (CORT) levels indicate that birds modify their stress response through the year. Although this has been well documented, the method by which birds achieve this seasonality is not well understood. In this study I used house sparrows to determine if changes in glucocorticoid receptor (GR) immunoreactivity in several stress-related brain nuclei showed seasonal variation. The house sparrowsshowed seasonal variation in their stress response with baseline CORT levels being highest during the breeding season and lowest during winter. There was also significant change in plasma CORT post-dexamethasone during breeding, but not during other times of the …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

Developmental Stress And The Effects On Physiological And Cognitive-Behavioural Traits In European Starlings, Tara M. Farrell

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Birdsong is a complex, learned vocalization that is a phenotypic expression of male quality. The developmental stress hypothesis describes how the cost to possessing a high quality song is paid in early development. Stressful early-life experiences have adverse effects on the development of the neural circuitry that regulates song learning and production, which results in a male advertising with a low quality song in adulthood. The purpose of this thesis was to test the developmental stress hypothesis in several respects in European starlings (Sturnus vulgaris). My objectives were to assess the long-term effects of developmental stress on (1) …

Non-Canonical Activation Of Nrf2 By Dimercaptopropanol As A Treatment For Huntington's Disease, Margaret Lauren Tindale

Electronic Thesis and Dissertation Repository

Mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels are strongly implicated in various neurodegenerative disorders, including Huntington’s disease (HD). Expression of the mutant Huntingtin protein (mHTT) containing an expanded polyglutamine repeat is associated with oxidative stress and toxicity in striatal neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for regulating expression of a diverse array of antioxidant and cytoprotective genes. Most known Nrf2-activating compounds act through the canonical pathway by mimicking a transient oxidative insult, and treatment effects are short-lived. This study reveals an increase in striatal cell viability, and a reduction in …

Mechanisms Of Neuroprotection Against Ischemic Insult By Stress-Inducible Phosphoprotein-1, Jason Xu

Electronic Thesis and Dissertation Repository

Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrP^C) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrP^C, α7nAChR, and ALK2 prior to oxygen-glucose deprivation …

Deep Brain Stimulation And Its Effects On Parkinson Disease Spatiotemporal Gait Parameters., Greydon Gilmore

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) alleviates common appendicular PD symptoms, such as: tremor, rigidity and bradykinesia. However, the effect STN-DBS has on modulating axial gait features has not been properly quantified objectively. The purpose of the present thesis was to investigate the role STN-DBS plays in modulating specific gait features such as pace, asymmetry, variability, rhythm and postural control. It is hypothesized that axial gait function is regulated predominantly by non-dopaminergic control systems. In the acute immediate post-operative phase a surgical effect, named the microlesion effect (MLE), is thought to produce a transient improvement of appendicular and axial symptoms. …

Laminar Fmri In Auditory Cortex At 7t, Jacob Jl Matthews

Electronic Thesis and Dissertation Repository

Auditory cortex is involved in the perception, attention, memory and imagery of sounds. Neuroimaging has been a rich source of information on which cortical areas are recruited for different tasks. However, a more detailed understanding has been confined to animal studies using invasive imaging modalities, and high-resolution functional descriptions of auditory cortex, including columnar/laminar specific activity, topographical organization within layers, and the way these representations transfer between processing structures remain poorly understood in humans. We present 7T fMRI as a non-invasive tool for high-resolution functional imaging of human auditory cortex on the laminar scale. We describe MATLAB tools for optimizing …

Determining Attention Deficits In Mouse Models Of Alzheimer’S Disease Using Touchscreen Systems, Talal Masood

Electronic Thesis and Dissertation Repository

Behavioural testing in mouse models of Alzheimer’s disease (AD) suffers from lack of standardization and reproducibility issues between laboratories. In order to solve this, a touchscreen system has been developed for mice based on the CANTAB. There are several cognitive dysfunctions that occur due to AD, including deficits in attention that can be tested using the touchscreens. In this study, we tested two mouse models of familial AD (5xFAD and 3xTG) with mutations that lead to an accelerated rate of amyloidosis. Both male and female mice were tested at two separate locations in order to test for the reproducibility of …

Structure-Function Relationship Of The Brain: A Comparison Between The 2d Classical Ising Model And The Generalized Ising Model, Pubuditha M. Abeyasinghe

Electronic Thesis and Dissertation Repository

There is evidence that the functional patterns of the brain observed at rest using fMRI are sustained by a structural architecture of axonal fiber bundles. As neuroimaging techniques advance with time, the relationship between structure and function has become the object of many studies in neuroscience. As recently suggested, the well defined connectivity structure found in the brain can be used to understand the self organization of the brain at rest, as well as to infer the functional connectivity patterns of the brain using different models, such as the Kuramoto model which studies synchronization, and the 2-dimensional classical Ising model, …

Neural And Behavioural Responses To Rewards And Losses In Early Development: A Functional Magnetic Resonance Imaging Study, Niki Hosseini-Kamkar

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) was used to investigate the neural and behavioural correlates of learning from rewards and losses in children. Greater blood-oxygen-level dependent (BOLD) responses in the ventral striatum (VS) and the ventromedial prefrontal cortex (VMPFC) were found when participants received rewards compared to when they missed out on an opportunity to receive rewards. In contrast, greater BOLD responses in the anterior insula (AI) and the anterior cingulate cortex (ACC) were found when participants received losses compared to when they avoided losing. The BOLD response to rewards in the VS and VMPFC correlated positively with the tendency to …

Developing A Contrast Agent For The In Vivo Detection Of Apoptosis, Mary R. Cobb

Electronic Thesis and Dissertation Repository

Currently, there is no way to assess apoptotic cell death in living organisms. We have developed a novel contrast agent targeted toward the detection of caspase-3 activity, the key enzymatic mediator of apoptosis. Our contrast agent consists of a dual magnetic resonance imaging/fluorescent probe coupled to a cell penetrating peptide (CPP) sequence by a peptide backbone containing a caspase-3 cleavage site. The CPP allows the agent to cross cell membranes and the blood brain barrier. In cells undergoing apoptosis, activated caspase-3 will cleave the agent removing the CPP and trapping the imaging probes inside the cell.

The purpose of this …

Co-Morbidity Of Alzheimer’S Disease And Stroke: Cognitive Deficits And Cellular Pathologies In Two Co-Morbid Animal Models, Jennifer L. Au

Electronic Thesis and Dissertation Repository

Prior to beta-amyloid (Aβ) protein accumulation into plaques in Alzheimer’s disease (AD), neuroinflammation and oxidative stress have been shown to contribute to early cognitive decline. These cellular pathologies are coincident in stroke, which is considered a risk factor for AD. This study investigated the co-morbid effects of AD and stroke on behavioural and cellular pathology in two rodent models. Motor function, memory and microglial neuroinflammation were investigated in a stroke and Aβ injection model and mutant human amyloid precursor protein (APP) transgenic model with stroke. Injections of endothelin-1 into the right striatum were used to model stroke and AD was …

Hierarchical Organization In Auditory Cortex Of The Cat Using High-Field Functional Magnetic Resonance Imaging, Amee J. Hall

Electronic Thesis and Dissertation Repository

Sensory localization within cortex is a widely accepted and documented principle. Within cortices dedicated to specific sensory information there is further organization. For example, in visual cortices a more detailed functional division and hierarchical organization has been recorded in detail. This organization starts with areas dedicated to analysis of simple visual stimuli. Areas higher in the organization are specialized for processing of progressively more complex stimuli. A similar hierarchical organization has been proposed within auditory cortex and a wealth of evidence supports this hypothesis. In the cat, the initial processing of simple auditory stimuli, such as pure tones, has been …

Muscarinic Attenuation Of Mnemonic Rule Representation In Macaque Dorsolateral Prefrontal Cortex During A Pro- And Anti-Saccade Task, Alex J. Major

Electronic Thesis and Dissertation Repository

Maintenance of context is necessary for execution of appropriate responses to diverse environmental stimuli. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in executive function, including working memory and representation of abstract rules, and is modulated by the ascending cholinergic system through nicotinic and muscarinic receptors. Muscarinic receptors’ effect on local primate DLPFC neural activity in vivo during cognitive tasks remains poorly understood. Here we examined the effects of muscarinic receptor blockade on rule-related activity in the macaque prefrontal cortex by combining iontophoretic application of the general muscarinic receptor antagonist scopolamine with single-unit recordings while monkeys performed a rule-guided …

Quantifying The Effects Of Systematic Stn-Dbs Programming On Rest And Postural Tremor In Idiopathic Parkinson Disease Patients, Kristina Ognjanovic

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is a complex neurodegenerative disorder that encompasses both motor and non-motor symptoms. These symptoms and their severity are typically assessed by scale based measures in a clinical setting. Scale- based assessments of PD patients undergoing bilateral subthalamic nucleus deep brain stimulation surgery (STN-DBS) such as the Unified Parkinson Disease Rating Scale (UPDRS) are commonly used in a clinical setting to assess symptom severity and progression. However, the subjective nature of these and other clinical scales call into question both the sensitivity and accuracy of patient assessment over time. An objective quantification of rest and postural tremor of …

Contribution Of The Dorsolateral Prefrontal Cortex To Attentional And Mnemonic Processes In Visual Search, Brandon Belbeck

Electronic Thesis and Dissertation Repository

A key characteristic of selective visual attention is that it may be deployed on the basis of our knowledge or goals of the task at hand. Here, we used cryogenic deactivation to investigate the contribution of the dorsolateral PFC to cognitive flexibility and working memory, as well as their relation to the deployment of attention. Macaque monkeys performed visual search tasks requiring them to foveate a target in an array of stimuli. These included a feature search, a constant-target conjunction search, a variable-target search and variable-target with delay search task, with each being more cognitively demanding than the last. Bilateral …

Modulation Of Synaptic Plasticity By Hippocampal Theta Rhythm, Clayton Law

Electronic Thesis and Dissertation Repository

The hippocampal theta rhythm facilitates memory formation. This study investigated the temporal relation of long-term potentiation (LTP) with the hippocampal theta rhythm. Theta rhythm consists of a wave of somatodendritic depolarization, but the depolarization of apical and basal dendrites of hippocampal CA1 pyramidal cells peak at a similar theta phase. Thus, we hypothesize that the population spike excitability evoked by excitation of the apical and basal dendrites peak at a similar phase of the theta rhythm. We also expect that LTP at the basal and apical dendritic synapses to be maximal at a similar theta phase.

Rats (~300 g) were …

A Kinematic Analysis Of Visual And Haptic Contributions To Precision Grasping In A Patient With Visual Form Agnosia And In Normally-Sighted Populations, Robert Whitwell

Electronic Thesis and Dissertation Repository

Skilled arm and hand movments designed to obtain and manipulate objects (prehension) is one of the defining features of primates. According to the two visual system hypothesis (TVSH) vision can be parsed into two systems: (1) the ventral ‘stream’ of the occipital and inferotemporal cortex which services visual perception and other cognitive functions and (2) the ‘dorsal stream’ of the occipital and posterior parietal cortex which services skilled, goal-directed actions such as prehension. A cornerstone of the TVSH is the ‘perception-action’ dissociation observed in patient DF who suffers from visual form agnosia following bilateral damage to her ventral stream. DF …

Category-Specific Item Recognition And The Medial Temporal Lobe, Christopher B. Martin

Electronic Thesis and Dissertation Repository

Much neuropsychological and neuroimaging research has been focused on the contributions of different medial temporal lobe (MTL) structures to recognition memory. The majority of these studies have linked perirhinal cortex (PrC) to item recognition, whereas the hippocampus and parahippocampal cortex (PhC) have primarily been associated with the recollection of contextual detail pertaining to a specific prior stimulus encounter. Here, I report results from three fMRI studies that examined the neural correlates of item recognition with a specific focus on the relationship between such signals and category-specific effects in the MTL. In Chapter 2, I reveal that category-specific representations in both …

The Relationship Between Dairy Product Consumption And Cognitive Performance In A Group Of Community-Dwelling Healthy Older Adults, Mariam R. Ismail

Electronic Thesis and Dissertation Repository

Dietary intake is one of the modifiable factors that may affect older adults’ cognitive function in their later years. Very little research has considered the potential role of dairy products on cognitive function. The aim of the present study was twofold: first, to investigate whether there is a difference in cognitive performance between older adults who consumed the recommended amount of dairy products (3 servings per day) and individuals who consumed less than the recommended amount (1 or 2 servings per day); second, to examine whether there is an association between the nutrients contained in the dairy products and cognitive …

Abnormal Hippocampal Activation In Freely Behaving Mice Deficient For The Vesicular Acetylcholine Transporter, Shahin Moallem

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Acetylcholine (Ach) has a fundamental role in cortical activation. The activation of the hippocampus, a cortex implicated in cognitive and sensorimotor functions, is characterized by an increase in power and frequency of oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range. We studied hippocampal activation in two mutant mouse lines with deficiency in cholinergic functionality: VAChT KD^HET (HET), and VAChT^{Nkx2.1-Cre-flox/flox} (KO). We hypothesized that the mutant mice, relative to wild-type (WT) mice, will manifest abnormal theta and gamma oscillations during different behaviors, and in response to muscarinic cholinergic antagonist scopolamine hydrochloride and to the NMDA …

Neural Correlates Of Spontaneous Bold Fluctuations: A Simultaneous Lfp-Fmri Investigation In The Non-Human Primate, Masoomeh Hashemi

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Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to explore functional connectivity (FC) between brain regions across neurological and psychiatric diseases. However, the neural basis of spontaneous low frequency blood-oxygen level dependent (BOLD) fluctuations is poorly understood.

Here, we acquired rs-fMRI data in macaque monkeys together with simultaneous recordings of local field potentials (LFPs) in prefrontal cortex area 9/46d. We first evaluated the correlation between LFPs (1-100 Hz) and BOLD signals and found unique frequency power correlates of positive and negative FC. Anti-correlation of high and low power envelopes indicated that ongoing cross-frequency interactions are a neural correlate of …

Mechanisms Of Neural Precursor Cell Apoptosis By Microglia-Derived Cytokines, Jennifer Guadagno

Electronic Thesis and Dissertation Repository

The persistence of neural precursor cells (NPCs) in distinct niches of the adult brain and spinal cord provides an important opportunity for regeneration in the affected nervous system. In the adult brain, neural precursor cells (NPCs) generate new neurons that can be integrated into the CNS circuitry to replace damaged or lost neurons, and contribute to learning and memory processes. Deregulated neurogenesis has been observed under both acute and chronic neurological conditions including stroke, Alzheimer’s disease, and Parkinson’s disease. The extent to which neurogenesis contributes to brain repair is severely limited by the neuroinflammatory processes associated with these neurodegenerative conditions. …

Resting-State Functional Network Disruptions In A Rodent Model Of Mesial Temporal Lobe Epilepsy (Tle), Ravnoor Singh Gill

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Mesial temporal lobe epilepsy (TLE) is the most common form of drug-refractory epilepsy. The clinical application of non-invasively mapped networks using resting-state functional magnetic resonance imaging (rsfMRI) in humans has been rather limited due to heterogeneous (varying etiology, drugs, onset, latent period, etc.) patient groups. We employed a pharmacological (kainic acid) rodent model of TLE to measure the extent of functional network disruptions using rsfMRI, and study selected behaviors and olfactory to hippocampus transmission. Graph theoretical network modelling and analysis revealed significant increase in functional connectivity connectivity to the temporal lobe (hippocampus) in epileptic-rats compared to controls in the limbic …