<p>Negotiating the complex decisions that we encounter daily requires coordinated neu- </p><p>ronal activity. The enormous variety of decisions we make, the intrinsic complexity </p><p>of the situations we encounter, and the extraordinary flexibility of our behaviors </p><p>suggest the existence of intricate neural mechanisms for negotiating contexts and </p><p>making choices. Further evidence for this prediction comes from the behavioral al- </p><p>terations observed in illness and after injury. Both clinical and scientific evidence </p><p>suggest that decision signals are carried by electrical neuronal activity and influenced </p><p>by neuromodulatory chemicals. This dissertation addresses the function of two puta- </p><p>tive contributors to decision-making: neuronal activity in posterior cingulate cortex </p><p>and modulatory effects of serotonin. I found that posterior cingulate neurons respond </p><p>phasically to salient events (informative cues; intentional saccades; and reward deliv- </p><p>ery) across multiple contexts. In addition, these neurons signal heuristically guided </p><p>choices across contexts in a gambling task. These observations suggest that posterior </p><p>cingulate neurons contribute to the detection and integration of salient information </p><p>necessary to transform event detection to expressed decisions. I also found that </p><p>lowering levels of the neuromodulator serotonin increased the probability of making </p><p>risky decisions in both monkeys and mice, suggesting that this neurotransmitter con- </p><p>tributes to preference formation across species. These results suggest that posterior </p><p>cingulate cortex and serotonin each contribute to decision formation. In addition, the </p><p>unique serotonergic pro jections to posterior cingulate cortex, as well as the frequent </p><p>implication of altered serotonergic and posterior cingulate function in psychiatric dis- </p><p>orders, suggest that the confluence of cingulate and serotonergic activity may offer </p><p>key insights into normal and pathological mechanisms of decision making.</p> / Dissertation

<p>Learning and memory is one of the critical components of the human experience. In one model of memory, hippocampal LTP, it is believed that the trafficking of AMPA receptors to the synapse is a fundamental process, yet the spatiotemporal kinetics of the process remain under dispute. In this work, we imaged the trafficking of AMPA receptors by combining two-photon glutamate uncaging on single spines with a fluorescent reporter for surface AMPA receptors. We found that AMPA receptors are trafficked to the spine at the same time as the spine size is increasing. Using a bleaching protocol, we found that the receptors that reach the spine come from a combination of the surface and endosomal pools. Imaging exocytosis in real time, we found that the exocytosis rate increases briefly (~1 min.), both in the spine and neighbouring dendrite. Finally, we performed pharmacological and genetic manipulations of signaling pathways, and found that the Ras-ERK signaling pathway is necessary for AMPAR exocytosis.</p> <p>In a set of related experiments, we also investigated the capacity of single spines to undergo potentiation multiple times. By stimulating spines twice using glutamate uncaging, we found that there is a refractory period for synaptic plasticity in spines during which they cannot further be potentiated. We furthermore found that inducing plasticity in a given spine inhibits plasticity at nearby spines.</p> / Dissertation

<p>The ultimate goal of the nervous systems of all animals is conceptually simple: Manipulate the external environment to maximize one's own survival and reproduction. The myriad means animals employ in pursuit of this goal are astoundingly complex, but constrained by common factors. For example, to ensure survival, all animals must acquire the necessary nutrients to sustain metabolism. Similarly, social interaction of some form is necessary for mating and reproduction. For some animals, the required social interaction goes far beyond that necessary for mating. Humans and many other primates exist in complex social environments, the navigation of which are essential for adaptive behavior. This dissertation is concerned with processes of transforming sensory stimuli regarding both nutritive and social information into motor commands pursuant to the goals of survival and reproduction. Specifically, this dissertation deals with these processes in the rhesus macaque. Using a task in which monkeys make decisions simultaneously weighing outcomes of fruit juices and images of familiar conspecifics, I have examined the neurophysiology of social and nutritive factors as they contribute to choice behavior; with the ultimate goal of understanding how these disparate factors are weighed against each other and combined to produce coherent motor commands that result in adaptive social interactions and the successful procurement of resources. I began my investigation in the lateral intraparietal cortex, a well-studied area of the primate brain implicated in visual attention, oculomotor planning and control, and reward processing. My findings indicate the lateral intraparietal cortex represents social and nutritive reward information in a common neural currency. That is, the summed value of social and nutritive outcomes is proportional to the firing rates of parietal neurons. I continued my investigation in the striatum, a large and functionally diverse subcortical nuclei implicated in motor processing, reward processing and learning. Here I find a different pattern of results. Striatal neurons generally encoded information about either social outcome or juice rewards, but not both, with a medial or lateral bias in the location of social or juice information encoding neurons, respectively. In further contrast to the lateral intraparietal cortex, the firing rates of striatal neurons coding social and nutritive outcome information is heterogeneous and not directly related to the value of the outcome. This dissertation represents a few incremental steps toward understanding how social information and the drive toward social interaction are incorporated with other motivators to influence behavior. Understanding this process is a necessary step for elucidating, treating, and preventing pathologies</p> / Dissertation

The neuropathology of Tourette Syndrome (TS) is poorly characterized. This thesis provides the first quantitative stereologic immunohistochemical study of the basal ganglia in TS. TS is a childhood neuropsychiatric disorder characterized by motor and vocal tics. Previous imaging studies found alterations in caudate (Cd) and putamen (Pt) volumes. To investigate possible alterations in cell populations, postmortem basal ganglia tissue from individuals with TS and normal controls (NC) was analyzed using unbiased stereological techniques. A markedly higher (>160% of control) total neuron number and density was found in the internal segment of the globus pallidus (GPi) of TS (p<0.025). An increased number (>220% of control) and proportion of these GPi neurons were positive for the calcium-binding protein parvalbumin (PV) in the tissue from TS subjects (p<0.025). In contrast, a lower number (<60% of control) of neurons was observed in the external segment (GPe) (p<0.025). In addition, there was a lower density of PV-positive interneurons in both Cd (<50% of control) and Pt (<65% of control) (p>0.025). The imbalance in striatal and GPi inhibitory neuron distribution suggests that the functional dynamics of cortico-striato-thalamic circuitry are fundamentally altered in severe, persistent TS.

Thesis (Ph.D.)--York University, 2008.. Graduate Programme in Computer Science and Engineering. / Typescript. Includes bibliographical references (leaves 267-287). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:NR45988

Title from title page of PDF (University of Missouri--St. Louis, viewed March 3, 2010). Includes bibliographical reference (p. 53-71).

Thesis (M.S.)--Western Washington University, 2010. / Includes bibliographical references (leaves 30-35). Also issued online.

published_or_final_version / Anatomy / Master / Master of Medical Sciences

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Not available