Neuroscience and Neurobiology Commons^™

Pdz Protein Regulation Of Β-Arrestin Recruitment And Gpcr Trafficking, Sarah Gupta

Electronic Thesis and Dissertation Repository

β-arrestins are versatile adaptor proteins that play a vital role in regulation of G protein coupled receptor (GPCR) trafficking and signalling properties. PDZ proteins have previously been shown to modulate β-arrestin2 recruitment and receptor internalization for many GPCRs including Corticotropin-Releasing Factor Receptor 1 (CRFR1), a receptor whose antagonists have been shown to demonstrate both anxiolytic- and antidepressant-like effects. Further characterization of the interplay between β-arrestins and PDZ proteins may aid in determining a potential mechanism for PDZ protein regulation of GPCR trafficking. Our findings suggest that PDZ proteins PSD-95, MAGI1, and PDZK1 complex with β-arrestin2 by interacting via the PDZ …

A Rat Model Of Cognitive Bias And The Effect Of Acute Corticosterone, Kai Wang

Electronic Thesis and Dissertation Repository

In humans, affective states can influence cognitive processes, resulting in a phenomenon referred to as “cognitive bias”. Rodents exhibit similar biases during the interpretation of ambiguous cues. It has been shown that cognitive bias shifts towards the negative valence (pessimism) when animals are under chronic stress manipulations. However, the effects of acute stress on cognitive bias have not been well established in an animal model. Here, a non-operant appetitive task using fluid rewards and distinct visual/tactile cues was developed to examine cognitive bias in male rats. Corticosterone was used to mimic stress levels similar to acute restraint stress. It was …

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR₁ and 5-HT_2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT_2A/CRs. The first purpose of this thesis was …

The Role Of Cholinergic Neurotransmission In Sensory Filtering And Sensorimotor Gating, Erin Azzopardi

Electronic Thesis and Dissertation Repository

At every moment, our brain is bombarded with sensory information. How we filter and process sensory information is critical for daily functioning and cognition. Examples of sensory filtering include habituation (a progressive decrease in responding) and prepulse inhibition (PPI, gating of responding). Our aim is to understand the differential role acetylcholine (ACh) plays in these processes.

To study this we used both reflexive (acoustic startle response: ASR) and non-reflexive (locomotor) behaviours. PPI is hypothesized to occur via inhibitory cholinergic projections from the Pedunculopontine Tegmental Nucleus (PPT) to the startle pathway. The role of ACh in habituation of reflexive and non-reflexive …

The Neural Mechanisms Of Musical Rhythm Processing: Cross-Cultural Differences And The Stages Of Beat Perception, Daniel J. Cameron

Electronic Thesis and Dissertation Repository

Music is a universal human behaviour, is fundamentally temporal, and has unique temporal properties. This thesis presents research on the cognitive neuroscience of the temporal aspects of music: rhythm, beat, and metre. Specifically, this work investigates how cultural experience influences behavioural and neural measures of rhythm processing, and the different neural mechanisms (with particular interest in the role of the striatum) that underlie different stages of beat perception, as musical rhythms unfold.

Chapter 1 presents an overview of the existing literature on the perceptual, cognitive, and neural processing of rhythm, including the entrainment of neural oscillations to rhythm and the …

Role Of Anterior Cingulate Cortex In Saccade Control, Sahand Babapoor-Farrokhran

Electronic Thesis and Dissertation Repository

Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. It has been postulated that prefrontal cortex is mainly involved in higher order cognitive functions. Specifically, anterior cingulate cortex (ACC), which is part of the prefrontal cortex, is suggested to be involved in performance monitoring and conflict monitoring that are considered to be cognitive control functions.

Saccades are the fast eye movements that align the fovea on the objects of interest in the environment. In this thesis, I have explored the role of ACC in control of saccadic eye movements. First, I performed …

Contribution Of The Primate Frontal Cortex To Eye Movements And Neuronal Activity In The Superior Colliculus, Tyler R. Peel

Electronic Thesis and Dissertation Repository

Humans and non-human primates must precisely align the eyes on an object to view it with high visual acuity. An important role of the oculomotor system is to generate accurate eye movements, such as saccades, toward a target. Given that each eye has only six muscles that rotate the eye in three degrees of freedom, this relatively simple volitional movement has allowed researchers to well-characterize the brain areas involved in their generation. In particular, the midbrain Superior Colliculus (SC), is recognized as having a primary role in the generation of visually-guided saccades via the integration of sensory and cognitive information. …

The Neuroprotective Effects Of Endurance Training On The Aging Brain, Katelyn Norton

Electronic Thesis and Dissertation Repository

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested …

Is Online Motor Control Really Impaired In Parkinson's Disease?, Kate E. Merritt

Electronic Thesis and Dissertation Repository

Patients with Parkinson’s disease (PD) are thought to be selectively impaired in consciously-mediated online automatic motor control, whereas the ability to perform subconscious online adjustments remains intact. This present study evaluates the hypothesis that the previously alleged deficits in online motor control in PD are not due to the consciousness of the correction, but rather are attributable to aspects of the prior experimental designs disproportionately penalizing patients for PD-related bradykinesia. Here, we implemented a modified traditional double-step paradigm to investigate consciously-mediated online motor control in PD, in a manner that would be unconfounded by disease-related bradykinesia. Further, we investigated the …

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT_2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the CRFR1 PDZ-binding motif. …

Spatial Memory In Black-Capped Chickadees: Studies Of Adult Hippocampal Neurogenesis And Win-Shift/Win-Stay Spatial Search, Nicole Ann Guitar

Electronic Thesis and Dissertation Repository

Two cognitive adaptations were studied in Black-capped chickadees through tests of adult hippocampal neurogenesis and Win-shift/Win-stay spatial search. Neurogenesis has been proposed to aid memory, therefore it was hypothesized that birds with decreased neurogenesis would perform poorer than controls in hippocampal-dependent spatial working and reference memory tasks followed by a reversal. Subjects with decreased neurogenesis, caused by the neurotoxin MAM, reversed slower than controls, suggesting that neurogenesis may contribute to differentiating similar memories, although this effect was nonsignificant. Win-shift/Win-stay foraging behavior is an adaptation to the replenishing and depleting nature of food. Since chickadees forage on food that depletes quickly …

Unravelling The Subfields Of The Hippocampal Head Using 7-Tesla Structural Mri, Jordan M. K. Dekraker

Electronic Thesis and Dissertation Repository

Probing the functions of human hippocampal subfields is a promising area of research in cognitive neuroscience. However, defining subfield borders in Magnetic Resonance Imaging (MRI) is challenging. Here, we present a user-guided, semi-automated protocol for segmenting hippocampal subfields on T2-weighted images obtained with 7-Tesla MRI. The protocol takes advantage of extant knowledge about regularities in hippocampal morphology and ontogeny that have not been systematically considered in prior related work. An image feature known as the hippocampal ‘dark band’ facilitates tracking of subfield continuities, allowing for unfolding and segmentation of convoluted hippocampal tissue. Initial results suggest that this protocol offers sufficient …

The Effects Of Concurrent Cognitive Load On The Processing Of Clear And Degraded Speech, Harrison Ritz

Electronic Thesis and Dissertation Repository

A previous study has found that perceiving degraded speech requires attention, with compromised behavioral and neurological measures of speech processing for degraded speech, but not clear speech, when participants are distracted (Wild et al., 2012b). We extended these findings by examining behavioral and neural correlates of speech perception under different levels of cognitive load using multiple object tracking. We also investigated the role of attention in perceiving degraded speech that was as intelligible as clear speech, in order to separate perceptual outcomes (i.e., intelligibility) from the requisite processing demands. We found that the speech perception system is heterogeneous in its …

The Behavioural Phenotype Of Pthr175-Tau Expression In The Hippocampus Of Female Adult Sprague Dawley Rats, Jason J. Gopaul

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis with cognitive impairment (ALSci) can be characterized by pathological inclusions of microtubule associated protein tau (tau) uniquely phosphorylated at Thr175 (pThr175-tau). The purpose of this study was to characterize the behavioural consequences of expressing a pseudophosphorylated tau mimic of pThr175-tau (Thr175Asp-tau) in rat hippocampus. Expression was hypothesized to lead to pathological tau fibril formation resulting in cognitive and behavioural deficits. Expression was accomplished in female Sprague Dawley rats through stereotactic inoculations of recombinant adeno-associated virus (rAAV9) vector with human tau gene. Pathological tau fibrillary structures were identified, but behavioural testing up to 12 months post-surgery revealed no …

Establishing An In Vivo Model For Intratumoral Modulation Therapy For Glioblastoma Multiforme, Mitchell D. Cooper

Electronic Thesis and Dissertation Repository

Glioblastoma multiforme (GBM) is the most common primary central nervous system tumor in adults, with an annual incidence of 3.0 per 100,000 of the population. Standard of care is a surgical resection of the tumor followed by adjuvant chemoradiation, but this treatment only offers patients a median lifespan of 12-18 months.

We propose an implanted device to deliver therapeutic high frequency electrical stimulation within the tumor-affected area of the brain, in a novel approach we refer to as Intratumoral Modulation Therapy (IMT). Our study aims to establish the effectiveness of this treatment in the F98 Fischer rat glioma model, a …

Pharmacogenetics Of Non-Motor Symptoms In Parkinson's Disease, Brian Robertson

Electronic Thesis and Dissertation Repository

Memory deficits are recognized in Parkinson’s disease (PD). The nature of these memory deficits is unclear because few studies have both isolated memory encoding and retrieval processes while testing patients on and off their dopamine replacement medication. Previous work suggests encoding depends upon regions innervated by the ventral tegmental area, which is relatively spared in PD, while retrieval depends upon dorsal striatum, which is dopamine deficient even early in PD. We investigated the impact of a dopamine transporter (DAT1), a dopamine reuptake protein, polymorphism (a 40-base-pair variable repeat affecting expression) on encoding and retrieval in healthy, elderly controls as well …

Sensory Filtering And Cognitive Function In A Valproic Acid Rat Model Of Autism, Theshani A. De Silva

Electronic Thesis and Dissertation Repository

Autistic individuals display sensory filtering impairments often correlated with cognitive dysfunction. Studies have shown that both these functions can be modulated by big potassium (BK) channels. Importantly, a subset of individuals with autism have shown BK channel mutations. We assessed sensory filtering and cognitive function through behavioural tests in a valproic acid (VPA) rat model of autism. We hypothesize that the model will display sensory filtering and cognitive impairments and that activation of BK channels may rescue observed cognitive deficits. Results revealed impairments in sensory filtering, hyper-locomotive activity and increased anxiety in VPA animals during adolescence. Although no significant impairments …

The Role Of Forebrain Cholinergic Signalling In Regulating Hippocampal Function And Neuropathology, Mohammed Al-Onaizi

Electronic Thesis and Dissertation Repository

Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric disorders, including Alzheimer’s Disease (AD). Cumulative use of drugs with anticholinergic activity is associated with increased risk for dementia and AD. Also, cholinergic function has been implicated in predicting the development of key neuropathological hallmarks seen in AD. However, the relationship between cholinergic dysfunction and conservation of cognitive ability as well as neuronal cell maintenance is not fully understood. Here, we tested how information processing and distinct molecular mechanisms associated with AD are regulated by cholinergic tone in genetically-modified mice in which cholinergic transmission was …

The Neural And Cognitive Basis Of Cumulative Lifetime Familiarity Assessment, Devin Duke

Electronic Thesis and Dissertation Repository

Perirhinal cortex (PrC) has been implicated as a brain region in the medial temporal lobes (MTL) that critically contributes to familiarity-based recognition memory, a process that allows for recognition to occur independently of contextual recollection. Informed by neurophysiological research in non-human primates, fMRI, as well as behavioural work in humans, the current thesis research tests the novel hypothesis that PrC cortex functioning also underlies the ability to assess cumulative lifetime familiarity with object concepts that are characterized by a lifetime of experiences. In Chapter 2, a patient (NB) with a left anterior temporal lobe (ATL) lesion that included PrC as …

Classifying Music Perception And Imagination Using Eeg, Avital Sternin

Electronic Thesis and Dissertation Repository

This study explored whether we could accurately classify perceived and imagined musical stimuli from EEG data. Successful EEG-based classification of what an individual is imagining could pave the way for novel communication techniques, such as brain-computer interfaces. We recorded EEG with a 64-channel BioSemi system while participants heard or imagined different musical stimuli. Using principal components analysis, we identified components common to both the perception and imagination conditions however, the time courses of the components did not allow for stimuli classification. We then applied deep learning techniques using a convolutional neural network. This technique enabled us to classify perception of …

Rethinking Resurrection: Choosing Interdisciplinary Dialogue Over Dualism, Jesse Dymond

Electronic Thesis and Dissertation Repository

Christianity is plagued by two dualistic concepts: first, an ontological dualism that divides the human person into body and soul, and second, an epistemological dualism that claims science and theology are incompatible. However, these polarized (and polarizing) theological frameworks are no longer sufficient, especially as scientific research provides new understanding about the brain and human identity. The existence of the nonphysical soul has long been called into question, thereby creating a theological crisis at the very core of Christian belief: the resurrection. This thesis will examine the crisis as it manifests itself in contemporary Christian society, pointing to the perpetuation …

Cannabinoid Cb1 Transmission In The Mesolimbic Reward Pathway, Tasha Ahmad

Electronic Thesis and Dissertation Repository

Cannabinoid CB1 receptor (CB1R) transmission within the mesocorticolimbic system plays an important role in forming associative memories, and processing both positive and negative experiences. Opiates generally produce potent rewarding effects and previous evidence suggests that CB1 transmission may modulate the neural reward circuitry involved in opiate reward processing. The ventral tegmental area (VTA), medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and Nucleus Accumbens (NA) are all implicated in opiate-reward processing, contain high levels of CB1 receptors, and are all modulated by dopamine (DA). Although, CB1 transmission within these areas has been heavily implicated in associative memory and learning, the potential …

Examining The Role Of Atrx In Astrocytes, Haley Mcconkey

Electronic Thesis and Dissertation Repository

Astrocytes perform many homeostatic roles in the brain while supplying metabolites to neurons and mediating synaptic transmission. The current study explored a possible role of the Atrx gene in astrocytes. Hypomorphic mutations in this gene cause the ATR-X intellectual disability syndrome. Deletion of Atrx in the forebrain leads to an apparent increase in reactive astrocytes, potentially caused by the high level of neuroprogenitor cell death. To avoid such non cell-autonomous effects on astrocytes, we generated mice with inducible conditional inactivation of Atrx in astrocytes. Preliminary analysis two weeks following induction of Atrx gene deletion revealed variably lower expression of Connexin …