Investigating the Role of PDE4D1/2 in Vascular Smooth Muscle Cell Desensitization

Thesis (Master, Biochemistry) -- Queen's University, 2016-10-14 02:44:01.604

ROLE OF THE FRONTAL EYE FIELD, SUPERIOR COLLICULUS, AND BASAL GANGLIA IN FLEXIBLE SACCADE BEHAVIOR

A distributed network of cortical and subcortical brain regions mediates the control of voluntary behavior, but it is unclear how this complex system may flexibly shift between different behavioral events. This thesis describes the neurophysiological changes in several key nuclei across the brain during flexible behavior, using saccadic eye movements in rhesus macaque monkeys. We examined five nuclei critical for saccade initiation and modulation: the frontal eye field (FEF) in the cerebral cortex, the subthalamic nucleus (STN), caudate nucleus (CD), and substantia nigra pars reticulata (SNr) in the basal ganglia (BG), and the superior colliculus (SC) in the midbrain. The first study tested whether a ‘threshold’ theory of how neuronal activity cues saccade initiation is consistent with the flexible control of behavior. The theory suggests there is a fixed level of FEF and SC neuronal activation at which saccades are initiated. Our results provide strong evidence against a fixed saccade threshold in either structure during flexible behavior, and indicate that threshold variability might depend on the level of inhibitory signals applied to the FEF or SC. The next two studies investigated the BG network as a likely candidate to modulate a saccade initiation mechanism, based on strong inhibitory output signals from the BG to the FEF and SC. We investigated the STN and CD (BG input), and the SNr (BG oculomotor output) to examine changes across the BG network. This revealed robust task-contingent shifts in BG signaling (Chapter 3), which uniquely impacted saccade initiation according to behavioral condition (Chapters 3 and 4). The thesis concludes with a published short review of the mechanistic effects of BG deep brain stimulation (Chapter 5), and a general discussion including proof of concept saccade behavioral changes in an MPTP-induced Parkinsonian model (Chapter 6). The studies presented here demonstrate that the conditions for saccade initiation by the FEF and SC vary according to behavioral condition, while simultaneously, large-scale task dependent shifts occur in BG signaling consistent with the observed modulation of FEF and SC activity. Taken together, these describe a mechanistic framework by which the cortico-BG loop may contribute to the flexible control of behavior.

CLASHES IN CONFINEMENT: MEN’S GENDERED EXPERIENCES WITH CONFLICT IN CANADIAN PRISONS

This dissertation presents the results of in-depth qualitative interviews with twenty-three formerly imprisoned men regarding their lived experience with prison conflict and the pain of incarceration. The results suggest that prison is a gendered ‘total institution’ (Goffman 1961). The pains that men experience in prison are uniquely gendered in that the deprivations imposed by incarceration– deprivation of autonomy, liberty, goods and services, heterosexual sex, and security (Sykes 1958) – in the reverse, define idealized masculinity as it is currently socially constructed: self-reliance, independence, toughness or invulnerability, material and economic success, and heterosexual prowess. From these shared deprivations emerges a gendered code of conduct that perpetuates a hierarchy among incarcerated men by constructing violent masculinity as a subcultural norm. The results suggest that the gender code in prison represents a set of rules that create opportunities for men to police each other’s gender performance and make claims to masculine statuses. Because status is inextricably tied to survival in this context, many men feel pressured to perform violent masculinities in prison despite privately subscribing to a non-violent sense of self-concept. The results suggest that violence is an expressive and instrumental resource for men in prison. A gender theory of prison violence, methodological findings, theoretical implications, ethical considerations and the short and long term aftermath of violent prison conflict are discussed.