Neuroscience and Neurobiology Commons^™

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 …

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 …

Taking Tone Into Account: Cognitive Neuroscientific Investigations Of Mandarin Chinese Spoken Word Processing, Jeffrey G. Malins

Electronic Thesis and Dissertation Repository

To date, theories of how humans recognize spoken words have yet to account for tonal languages such as Mandarin Chinese. One reason for this is that we know relatively little about how native speakers of tonal languages process spoken words in the brain. This dissertation addresses this problem by examining Mandarin spoken word processing in both adult native speakers and typically developing children. In adults, functional magnetic resonance imaging (fMRI) was used to assess the extent to which the brain regions involved in processing tonal information are distinct from those involved in vowel processing (Chapter 2), while event related potentials …

Investigation Of Sox9 Ablation On Neural Stem Cell Behaviour After Spinal Cord Injury, Stephen Mcdonald

Electronic Thesis and Dissertation Repository

After spinal cord injury neural stem cells are activated to proliferate and differentiate primarily into astrocytes, but are unable to replace lost neurons or aid in neurological recovery. Recent research shows that the transcription factor Sox9 promotes gliogenesis while inhibiting neurogenesis, and that Sox9 ablation causes improved recovery after spinal cord injury. The purpose of this study was to determine how Sox9 ablation alters neural stem cell behaviour after spinal cord injury and whether it leads to neurological improvements. We used BrdU and YFP to label and track neural stem cells and a neural stem cell-specific Sox9 knockout mouse model …

Neural Circuits Involved In Mental Arithmetic: Evidence From Customized Arithmetic Training, Christian Battista

Electronic Thesis and Dissertation Repository

An arithmetic training study was conducted using a novel paradigm known as Customized Arithmetic Training (CAT). Using the CAT system, self-reports obtained from the participants were used to generate individually tailored problem sets. These problem sets balanced strategy use such that each participant started with an equal amount of problems solved by fact retrieval (e.g., 2 + 2 = 4) and an equal amount of problems solved by procedural calculation (e.g., 34 + 37). Following the training period, participants solved trained and untrained problems from their customized arithmetic sets while undergoing an fMRI scan, after which they again provided self-reported …

Testing The Template Hypothesis Of Vocal Learning In Songbirds., Adriana Diez

Electronic Thesis and Dissertation Repository

The auditory forebrain regions NCM and CMM of songbirds are associated with perception and complex auditory processing. Expression of the immediate-early gene ZENK varies in response to different sounds. Two hypotheses are proposed for this. First, ZENK may reflect access to a representation of song memories. Second, ZENK may reflect attention. I tested these hypotheses by measuring ZENK in response to tutored heterospecific or isolate songs compared to non-tutored wild-type song. Young zebra finch females were exposed to different tutoring conditions and later exposed to different playbacks, and the expression of ZENK in CMM and NCM measured. ZENK responses varied …

Cortical Cannabinoid Modulation Of Subcortical Dopamine Activity: Implications For Emotional Processing, Brittany Draycott

Electronic Thesis and Dissertation Repository

Humans receive countless sensory inputs from the outside world to which they assign a certain level of emotional significance. However, there are times when an individual may assign an abnormally high level of emotional salience to an otherwise non-significant event, resulting in an inappropriate allocation of attention as seen in the hallucinations and psychosis associated with schizophrenia. Several brain regions are involved in this emotional processing, including the medial prefrontal cortex (mPFC) and the ventral tegmental area (VTA). We have previously shown that activation of mPFC cannabinoid (CB1) receptors in rats causes a potentiated fear response to a normally non-salient …

Investigating The Pathological Response To Beta Amyloid Toxicity In Rats: The Role Of Age And The Antioxidant Catalase-Skl, Hayley J. Nell

Electronic Thesis and Dissertation Repository

Accumulation of beta-amyloid (Aβ) in the brain is a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer’s disease (AD). In part, Aβ exerts its toxic effects by increasing reactive oxygen species (ROS) and neuroinflammation in the brain. Aging, a major risk factor for AD is also associated with increased production of ROS. This study investigated the age-related pathological response to Aβ toxicity and examined whether catalase-SKL(CAT-SKL), a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase, is able to reduce Aβ toxicity. Bilateral intracerebroventricular (icv) injections of the Aβ_25-35 peptide was used to model Aβ …

Cognitive Roles Of Anterior And Posterior Pedunculopontine Tegmentum Subregions, Jordan C. Robinson

Electronic Thesis and Dissertation Repository

The pedunculopontine tegmentum (PPT) is part of the mesopontine cholinergic system with distinct anterior and posterior subdivisions. With fast sensory input and descending connections to brainstem locomotor centers, we predict posterior PPT (pPPT) mediates prepulse inhibition of acoustic startle reflex, a form of sensorimotor gating that affects attentional processes. Similar to pPPT cholinergic projections to ventral tegmental area, we predict anterior PPT cholinergic input to substantia nigra regulates dopamine release in striatum, which is important for reinforcement learning. We lesioned the PPT bilaterally in male Sprague Dawley rats with ibotenic acid. Posterior cholinergic cell loss was significantly correlated with prepulse …

A P300 Based Cognitive Assessment Battery For Severely Motor-Impaired And Overtly Non-Responsive Patients, Aaron M. Kirschner

Electronic Thesis and Dissertation Repository

Diagnosing disorders of consciousness (DOC) is notoriously difficult, with estimates of misdiagnosis rates as high as 40%. Moreover, recent studies have demonstrated that patients who do not show signs of volitional motor responses can exhibit preserved command following detected by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although these patients clearly retain some cognitive abilities, lack of consistent motor responses makes administration of standard neuropsychological tests impossible. Consequently, the extent of their cognitive function is unknown. In the current study, we developed and validated a P300b event related potential (ERP) neuropsychological battery in healthy participants to assess components of …

Investigation Of Auditory Encoding And The Use Of Auditory Feedback During Speech Production, Laura E. Beamish

Electronic Thesis and Dissertation Repository

Responses to altered auditory feedback during speech production are highly variable. The extent to which auditory encoding influences this varied use is not well understood. Thirty-nine normal hearing adults completed a first formant (F1) manipulation paradigm where F1 of the vowel /ε/ was shifted upwards in frequency towards an /æ/–like vowel in real-time. Frequency following responses (FFRs) and envelope following responses (EFRs) were used to measure neuronal activity to the same vowels produced by the participant and a prototypical talker. Cochlear tuning, measured by SFOAEs and a psychophysical method, was also recorded. Results showed that average F1 production changed to …

Toxin-Induced Gustatory Conditioning In Rats: Examining The Effects Of Low Dose Toxins In Food On Rat Feeding Behaviour And Avoidance Conditioning, Amber N. Good

Electronic Thesis and Dissertation Repository

Foraging animals must learn which foods in their environment will maximize their nutritional needs but minimize the amount of ingested toxins. These animals rely on the integration of sensory and gustatory information and post-ingestive feedback from the foods they consume. Gustatory conditioning can be studied by using the conditioned taste avoidance paradigm and the toxin LiCl. This thesis first examined the dose related effects of low levels of LiCl on the ingestion of different palatable sucrose and salt solutions. The present findings support the hypothesis that rats use a behavioural tolerance mechanism to regulate their intake of foods containing low …

Spinal Cord Control Of Ejaculatory Reflexes In Male Rats, Natalie Kozyrev

Electronic Thesis and Dissertation Repository

Ejaculatory dysfunction impacts large numbers of men of all ages and around the world. In addition, a great majority of men with chronic spinal cord injury (SCI) experience ejaculatory dysfunction, which negatively impacts the quality of life of these individuals and their partners. SCI men emphasize the significance of regaining sexual function as their main goal. Currently, there is a marked absence of literature reporting the alterations to sexual function and ejaculation in particular in animal models of chronic SCI. In addition, there are many unanswered questions pertaining to the spinal cord control of ejaculation in healthy, intact men. It …

The Influence Of Proficiency And Age Of Acquisition On Second Language Processing: An Fmri Study Of Mandarin-English Bilinguals, Emily S. Nichols

Electronic Thesis and Dissertation Repository

Research investigating the neural correlates of second language (L2) processing has usually studied age of acquisition (AoA) and proficiency separately. Presently, we examined both in parallel, treated as continuous variables. We used fMRI to study neural activity for L2 processing in adult native Mandarin speakers who are L2 English speakers. Behavioral measures of language proficiency and AoA were obtained from subjects prior to performing a picture-word matching task during an fMRI scan. Brain activity during L2 English processing was shown to be independently affected by AoA and proficiency; activity in left superior temporal gyrus and right parahippocampal gyrus was modulated …

Reorganization Of Inhibitory Synapses In Experimental Epilepsy, Emily J. Pollock

Electronic Thesis and Dissertation Repository

The integrity and stability of interneurons in a cortical network is essential for proper network function. Loss of interneuron synaptic stability and precise organization can lead to disruptions in the excitation/inhibition balance, a characteristic of epilepsy. This study aimed to identify alterations to the GABAergic interneuron network in the piriform cortex (PC: a cortical area believed to be involved in the development of seizures) after kindling-induced seizures. Immunohistochemistry was used to mark perineuronal nets (PNNs: structures in the extracellular matrix that provide synaptic stability and restrict reorganization of inhibitory interneurons) and interneuron nerve terminals in control and kindled tissue. Results …

The Role Of Α5gaba(A) Receptors In Brain Inflammation, Jason K. Wong

Electronic Thesis and Dissertation Repository

Microglia critically regulate brain inflammation. GABA_A receptors that contain the α5-subunit (α5GABA_A) exhibit high sensitivity to GABA and confer tonic activity. Moreover, α5GABA­_A receptors have been associated with brain inflammation. This study investigates the role of α5GABA_A receptors in microglial activation. Immunohistochemistry revealed that in response to intraperitoneal lipopolysaccharide (LPS), α5-subunit null mice exhibited significantly higher expression of IL-1β in hippocampal microglia. Neuronal-glial co-cultures treated with α5GABA­_A receptor inverse agonist L655,708 drastically increased microglial IL-1β expression. Surprisingly, ELISA of media from L655,708-treated co-cultures revealed a considerably lower concentration of IL-1β. Treating cultured primary astrocytes …

Dopamine Modulation Of Emotional Learning In The Medial Prefrontal Cortex, Nicole M. Lauzon

Electronic Thesis and Dissertation Repository

Dopamine (DA) transmission plays a critical role in the processing of emotionally salient information and in associative learning and memory processes. Within the mammalian brain, neurons within the medial prefrontal cortex (mPFC) are involved critically in the encoding, expression, and extinction of emotionally salient learned information. Within the mPFC, DAergic transmission is involved importantly in controlling attention related and motivational processes, particularly within the context of emotionally salient sensory information. Considerable evidence suggests differential roles for DA D₁-like versus D₂-like receptors, including the D₄-receptor subtype, in the regulation of neuronal activity and emotional processing …

Flexibly Adapting To Emotional Cues: Examining The Functional And Structural Correlates Of Emotional Reactivity And Emotion Control In Healthy And Depressed Individuals, Steven G. Greening

Electronic Thesis and Dissertation Repository

The ability of emotionally significant stimuli to bias our behaviour is an evolutionarily adaptive phenomenon. However, sometimes emotions become excessive, inappropriate, and even pathological, like in major depressive disorder (MDD). Emotional flexibility includes both the neural processes involved in reacting to, or representing, emotional significance, and those involved in controlling emotional reactivity. MDD represents a potentially distinct form of emotion (in)flexibility, and therefore offers a unique perspective for understanding both the integration of conflicting emotional cues and the neural regions involved in actively controlling emotional systems.

The present investigation of emotional flexibility began by considering the functional neural correlates of …

Cognitive Function In Bk Channel Knock-Out Mice, Magdalena N. Mirkowski

Electronic Thesis and Dissertation Repository

BK channels are large conductance potassium channels activated by both Ca²⁺ concentration and membrane depolarization. They recently have been implicated to be involved in sensorimotor gating and higher cognitive function. However, it is not yet clear to what extent these channels affect these functions. The purpose of this study is to assess the role of BK channels in sensorimotor gating and cognitive function. We used a C57BL6 and SV129 hybrid mouse model in which the pore forming alpha subunit was genetically deleted. We employed the acoustic startle response to assess mechanisms of sensory gating (habituation and PPI), and the …

Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …

From Armchair To Wheelchair: How Patients With A Locked-In Syndrome Integrate Bodily Changes In Experienced Identity, Marie-Christine Nizzi

Future Directions in Feminist Phenomenology

No abstract provided.

Feminist Phenomenology, Embedded Embodied Cognition, And [Pseudo] Scientific Gender Claims, Veronica Vasterling

Future Directions in Feminist Phenomenology

No abstract provided.

Magnetic Resonance Imaging Of Brain Tissue Abnormalities: Transverse Relaxation Time In Autism And Tourette Syndrome And Development Of A Novel Whole-Brain Myelin Mapping Technique, Yann Gagnon

Electronic Thesis and Dissertation Repository

The transverse relaxation time (T2) is a fundamental parameter of magnetic resonance imaging sensitive to tissue microstructure and water content, thus offering a non-invasive approach to evaluate abnormalities of brain tissue in-vivo. Prevailing hypotheses of two childhood psychiatric disorders were tested using quantitative T2 imaging and automated region of interest (ROI) analyses. In autism, the under-connectivity theory, which proposes aberrant connectivity within white matter (WM) was assessed, finding T2 to be eleveted in the frontal and parietal lobes, while dividing whole brain data into neurodevelopmentally relevant WM ROIs found increased T2 in bridging and radiate WM. In Tourette syndrome, tissue …

Exploring The Neural Basis Of Top-Down Guided Action In Macaque Monkeys, Jessica M. Phillips

Electronic Thesis and Dissertation Repository

To thoroughly characterize any brain mechanism requires an appropriate animal model for invasive studies. An invaluable model system used toward a comprehension of cognitive neurophysiology is the macaque monkey. It is important to delineate similarities and limitations for this model in relation to the human brain and cognition. In this thesis, we have thus conducted three experiments to investigate putative generalizations between monkeys and humans regarding the neural processes associated with top-down action control in monkeys.

Our daily behaviour is largely comprised of automatic routine actions. The frequent repetition of certain behaviours in response to particular contexts can give rise …

Circadian Rhythms In Reward And Underlying Neural Circuits, Ricardo M. Baltazar

Electronic Thesis and Dissertation Repository

Studies suggest that the circadian timing system exerts an important influence on responses to rewarding stimuli. Diurnal rhythms in the rewarding value of amphetamine and mating behavior were observed, but differed in the pattern of their timing. Daily fluctuations in reward were correlated with oscillations in mesolimbic dopaminergic activity in both the nucleus accumbens (NAc) and ventral tegmental area (VTA), with a peak in NAc coinciding with the peak of sex reward, while the peak in the VTA associated with the peak in amphetamine reward. Also, rhythmic expression of the marker of neural activation, cFos, was observed in NAc, medial …

Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung

Physiology and Pharmacology Publications

Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but …