Browsing by Subject "Cortex"
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Item Astrocytes in alcohol use disorder(2020-05-08) Erickson, Emma Kerstin; Harris, R. Adron; Mayfield, R. Dayne (Roy Dayne), 1958-; Contreras, Lydia M; Eberhart, Johann K; Iyer, Vishwanath RExcessive alcohol use causes abundant molecular adaptations throughout the brain, contributing to the pathology of alcohol use disorders (AUDs). Over 50 years of alcohol research has provided insight into brain regions and neurotransmitter systems associated with the development and maintenance of addiction. However, the cellular specificity of alcohol-related functional changes and their contributions to the neurobiology of AUDs remain largely unknown. In addition to neurons, a large percentage of brain space is occupied by glial cells, including astrocytes. Until recently, astrocytes were thought to be simple, passive support cells with no significant impact on behavior. This philosophy has begun to fade with new data demonstrating astrocytes are actively involved in regulating brain function and have the potential to be critical modulators of brain disorders like addiction. In this dissertation, I investigate the role of astrocytes in alcohol-induced molecular adaptations and behaviors. In the first two sections, I present transcriptome signatures of astrocytes isolated from mice subjected to different mouse models of AUD. I identify important biological pathways affected by alcohol that could disrupt cellular function. In the next section, I reveal astrocyte involvement in alcohol consumption and intoxication. Finally, I explore how astrocyte function affects acute behavioral responses to ketamine, a drug with similar molecular pharmacology as ethanol. Altogether, this work uncovers novel roles for astrocytes in behavioral responses to drugs while offering an array of promising astrocyte-specific molecular targets for future interrogation.Item Circuit mechanisms of persistent activity in the primate cortex during working memory(2019-05-13) Hart, Eric Lewis; Huk, Alexander C.; Hayhoe, Mary M; Mauk, Michael; Nauhaus, Ian M; Aldrich, Richard WWorking memory is the cognitive ability to actively maintain and manipulate information on the timescale of seconds. Neurons in the prefrontal and posterior parietal cortices of the primate brain remain active in absence of sensory input and appear to correlate with working memory. In this thesis, I investigate the mechanisms of persistent activity during working memory in the frontoparietal network of the macaque. By conducting simultaneous electrophysiological recordings in two of the key regions of this network, the lateral intraparietal area (LIP) and the frontal eye fields (FEF), and employing statistical models of the neural population activity, I characterized the interactions between neurons locally in each area and between these two distant brain regions. In a visuospatial working memory task, during which the subject must remember the spatial location of a target, I found strong recurrent activity on single trials both within and between these areas that was not due to the visual stimulus or the motor response. The strength and timescale of functional interactions between LIP and FEF were highly reciprocal and symmetrical, providing evidence for the theory that reverberatory activity in this circuit does, in fact, support working memory. However, contrary to current models of the frontoparietal network, area LIP exhibited greater local recurrent excitatory activity than FEF, and many individual neurons in LIP displayed activity on longer timescales. In addition, the concurrent population activity had a greater impact on the spiking activity of most neurons than each individual neuron’s own intrinsic drive, especially in LIP. This result further emphasizes the role of network mechanisms in generating and maintaining persistent activity. Taken together, these findings suggest revisions to the current models of working memory, and highlight the importance of studying population activity on single trials.Item A comparative study of cortical computations in the mammalian visual cortex(2015-05) Scholl, Benjamin Kyle; Priebe, Nicholas; Geisler, Wilson S; Aldrich, Richard W; Pillow, Jonathan W; Hirsch, Judith AA common feature of all mammals is the cerebral cortex, which is essential for higher-order functions and processing information to generate motor actions. While cortical circuits exhibit a striking uniformity in anatomical organization, it is unknown whether these circuits preform similar computations across mammalian species. In this dissertation I compare the emergence of two computations in the primary visual cortex (V1) of carnivores and rodents. A cortical computation is a transformation in neural representation, such that the spiking output of a cortical neuron exhibits a selectivity not present in the inputs from upstream neurons. Here I explore two computations: orientation selectivity, the preference of neurons for oriented edges in the visual world, and binocularity, the integration of signals from the two eyes. In the first section, I compare the emergence of orientation selectivity in the early visual pathway of mouse and cat. Recordings from thalamic relay cells and V1 neurons in both species reveal orientation selectivity in mouse V1 is not emergent, and could be inherited subcortically. In a second set of experiments, I measure orientation selectivity and the organization of V1 orientation preference in a grasshopper mouse with predatory behavior, compared to the scavenger lab mouse. Here I find the same functional properties. In the second section, I focus on the integration of ocular inputs in V1 of mouse and cat. I first compare disparity selectivity in cats, where convergence of ocular inputs has long been established, with mice, where ocular integration had not previously been investigated. Similar to cats, mouse V1 neurons were sensitive to binocular disparity, albeit to a lesser degree, and could be described by a linear feed-forward model. I next explore the disruption of binocular disparity tuning in both animals. In cats, strabismus induced during development causes increased monocularity in V1 and a loss of disparity selectivity. In mice, monocular deprivation causes increased ocular input, which also manifests as decreased disparity selectivity. Finally, I explore how excitatory and inhibitory neurons in mouse V1 integrate binocular signals. Paravalbumin-expressing inhibitory interneurons are more binocular but less disparity tuned than surrounding cortical neurons, providing a canonical mechanism explaining loss of disparity selectivity in both carnivores and rodents.Item Cortical hemodynamics and motor recovery after cortical infarcts(2015-05) Woodie, Daniel Aaron; Jones, Theresa A.; Dunn, Andrew KStroke is the leading cause of disability and the fourth leading cause of death in the United States. Of those that survive a stroke, many are left with long term functional motor impairments. Spontaneous recovery of motor function occurs after a stroke and the reorganization of spared neural tissue is a contributing factor. To study motor recovery following a stroke, rodent models have been especially useful because experimental manipulations can be paired with controlled infarcts to understand physiologically relevant changes. For example, stroke to the sensory-motor cortex (SMC) in mice produces functional motor impairments which are dependent on the reorganization of the remaining cortex. Ironically, after about 20 years of research on the reorganization of the peri-lesion following cortical ischemia, there has been a lack of focus on the neuro-vascular changes as they relate to functional outcome after stroke. The central hypothesis of this report is that spontaneous vascular remodeling contributes to behavioral recovery and cortical reorganization following ischemic insult. To investigate the relationship between blood flow recovery and improvement of motor function after an ischemic insult, we developed a mouse model of upper extremity impairment after a stroke that can be repeatedly imaged in vivo. Specifically, 14 C57/BL6 mice either received photo-thrombotic cortical lesions (n=7) or vehicle procedures (n=7), were allowed 3 days to recover, and then received forelimb function probes using the pasta matrix reaching task (PMRT), an assay for skilled forelimb function, in tandem with the imaging of cortical blood flow using multi-exposure speckle imaging (MESI) at Days 3, 5, 10, and 20. Results indicate that the mice that received injections with Rose Bengal displayed significantly decreased performance on the PMRT and a significantly reduced amount of cortical blood flow compared to both their baseline performance and the control group. Skilled forelimb performance following the ischemic lesion correlated strongly with stroke severity (as indexed by cortical blood flow in the lesion core 2 hours following lesion induction). Additionally, the re-establishment of cortical blood flow to the infarct core precedes the recovery of motor performance, indicating potential importance for the re-establishment of blood flow to support the adaptive plasticity required for motor recovery.Item Extending PrAGMATiC : modeling covariances between responses across the human cortex(2021-05-07) Noble Hernandez, Daniel Alejandro; Huth, Alexander G.The human brain can be understood and organised as a topographic map of cortical areas. Dividing the brain into these distinct subsections has long been an ongoing effort, with a number of often disagreeing attempts to create this map – representative across individuals – being made over time. Both surgical and computational techniques have been broadly utilized in this pursuit, focusing on characterizing these chosen cortical areas based on their structural and functional similarities across individuals. Because the general anatomy is fairly well-understood now, computational methods are favoured; a popular approach taken involves measuring the responses of areas of the cortex according to functional magnetic resonance imaging (fMRI) data. We take a related – but modified – approach in this paper, delineating a model that uses the covariances oof the responses across the cortex rather than the cortical responses themselves. An extension of the existing hierarchical, Bayesian, probabilistic and generative model PrAGMATiC, our mathematical formulation of the model assumes and samples from an underlying Wishart, rather than Gaussian, distribution. This will allow the model to learn parameters to describe the functional covariances of responses at vertices across the cortex. Since direct comparisons of functional values, rather than their covariances, are not readily achieved in resting state fMRI, this formulation will be able to identify cortical parcellations using resting state fMRI data by providing a framework under which comparisons are possible.