The ventromedial hypothalamic nucleus (VMH) is an important central effector site involved in activating brown adipose tissue (BAT) or non-shivering thermogenesis. VMH neurons have previously been shown to be thermally responsive to changes in local temperature of the preoptic area/anterior hypothalamus (PO/AH). However, the thermoresponsiveness of VMH neurons of room temperature acclimatized and cold acclimatized rats to peripheral thermal stimulation has not been tested. In this thesis, a series of studies was designed to determine the thermoresponsiveness of VMH neurons to peripheral (scrotal) thermal stimulation of rats. Extracelluiar VMH neuronal activity was recorded from urethane anaesthetized male Sprague-Dawley rats, which were acclimatized either to room temperature (21°C for 4 weeks) or to cold (4°C for 4 weeks) prior to testing, during scrotal cooling and heating with glass-micropipettes filled with 0.5 M sodium acetate containing 2% pontamine sky blue. The rats' colonic temperatures were kept at normothermia (37°C), or hypothermia (33-35°C) during scrotal thermal stimulation. In the room temperature acclimatized rats, VMH neurons were temperature responsive to scrotal heating and cooling and were classified as warm responsive (WRN), cold responsive (CRN) and temperature non-responsive neurons (TNRN), based on their thermal coefficients. The ratio of VMH WRNs and CRNs was similar to that of thermoresponsive neurons observed in other brain regions (eg, the PO/AH and thalamus). VMH WRNs and CRNs were further classified as biphasic or monophasic in nature according to their thermal responses to scrotal heating and cooling. VMH neurons sustained their thermoresponsiveness to repeated trials of scrotal thermal stimulation with colonic temperatures maintained at 37°C or when colonic temperatures were acutely lowered from 37°C to 35°C and 33°C. In addition, scrotal thermal signals specifically altered neuronal activity of VMH thermoresponsive neurons, as changes in EEG activity did not occur with changes in VMH neuronal activity. Scrotal thermal inputs were functionally shown to be transmitted via the medial preoptic nucleus (MPO) prior to reaching the VMH nucleus because thermoresponsive VMH neuronal activity was blocked with the pretreatment of lidocaine into the MPO. Scrotal heating or cooling to 21°C-acclimatized rats did not increase IBAT temperatures, inferring that scrotal cooling had not evoked IBAT thermogenesis in this group. In cold acclimatized (CA) rats, prolonged (over 2 hours) and transient localized scrotal cooling caused IBAT temperatures to increase, inferring that scrotal cooling activated BAT thermogenesis. Mean basal firing rates of all recorded VMH neurons of CA-groups significantly increased, compared to those of VMH neurons observed in room temperature acclimatized (RA) groups. More VMH CRNs than WRNs were recorded in the CA-group and the thermoresponsiveness (ie, thermal coefficient) of VMH CRNs significantly increased during localized scrotal cooling in the cold acclimatized group, compared to thermal coefficients of VMH CRNs of the RA-groups. (Abstract shortened by UMI.)

We constructed a model of the coordination of segmental heart motor neurons driving blood circulation in leeches. The heart motor neuron models were conductance-based; conductances of voltage-gated and synaptic currents were adjusted to match the firing pattern of heart motor neurons from the living system. Each motor neuron receives a specific pattern of inhibitory input from rhythmic premotor heart interneurons and translates this spatiotemporal pattern into the fictive heartbeat motor pattern. The temporal pattern of synaptic input to the model was derived from extracellularly recorded spikes of the premotor heart interneurons. We focused on determining the components necessary to produce side-to-side asymmetry in the motor pattern: motor neurons on one side fire nearly in synchrony (synchronous coordination), while on the other they fire in a rear-to-front progression (peristaltic coordination). The model reproduces the general trends in phasing and was used to investigate the effective contribution of several synaptic and cellular properties of the motor neurons. The spatial and temporal pattern of premotor synaptic input, the electrical coupling between the segmental motor neurons, intra-burst, short-term synaptic plasticity of the synaptic inputs, and the axonal conduction delays all were integrated with the intrinsic membrane properties to influence intersegmental phasing.

Modern neuron models are large, complex entities. The ability to better simulate these complex models has been iven by the development of ever more powerful and cheap computers. The capacity to manage and understand the models has lagged behind improvements in simulation ability almost from the inception of neuron modeling. Despite the computing power currently available, more powerful simulation platforms and strategies are needed to cope with current and next generation neuron models. This thesis develops methodologies aimed at better characterizing motoneuron models. The hypothesis presented is that relationships between model outputs in addition to the relationships between model inputs (parameters) and outputs (behaviors) provide a characteristic description of the model that describes the model in a more useful way than just model behaviors. This description can be used to compare a model to different implementations of the same motoneuron and to experiment data. Data mining and data reduction techniques were used to process the data. Principal component analysis was used to indicate a significant, consistent reduction in dimensionality in an intermediate, mechanistic layer between model inputs and outputs. This layer represents the non-linear relationships between input and output, implying that if the non-linear relationships of a model were better understood and accessible, a model could be manipulated by varying the mechanism layer members, or rather the model parameters that primarily affect a mechanism layer member. Hierarchical cluster analysis showed similarity between sensitivity analyses data from models with random parameter sets. A main cluster represented the main region of model behavior with outlying clusters representing non-physiological behavior. This indicates that sensitivity analysis data is a good candidate for a model signature. The results demonstrate the usefulness of cluster analysis in identifying the similarities between data used as a model characterization metric or model signature. Its application is also valuable in identifying the main region of useful activity of a model, thus helping to identify a potential 'average' parameter set. Furthermore, factor analysis also proves functional in identifying members of the mechanism layer as well as the degree to which model outputs are affected by these members.

<p>Cognition has for a long time been viewed as a process that can be described in terms of computational symbol manipulation, i.e. a process that takes place inside people’s heads and is largely unaffected by contextual aspects. In recent years, however, there has been a considerable change in the way researchers look at and study human cognition. These changes also have far-reaching implications for education and educational research. Situated learning is a theoretical framework in which sociocultural aspects of cognition and learning are strongly emphasised, that is, the context in which learning takes place is an important part of learning activity. The concept of activity is central to situated learning theories, but activity has been considered an exclusively sociocultural process in which the body only plays a minor role. In embodied cognition research, on the other hand, there is an increasing awareness that mind and body are inextricably intertwined and cannot be viewed in isolation. Findings in cognitive neuroscience provide additional evidence that cognition is tightly linked to perception and action. The aim of this thesis has been to investigate the role of the body in situated learning activity by integrating these different perspectives on cognition and learning. The analysis suggests that, like individual human conceptualization and thought, situated learning is in fact deeply rooted in bodily activity. In social interactions the body provides individuals with a similar perspective on the world, it functions as a means of signalling to others what cannot (yet) be expressed verbally, and it serves as a resonance mechanism in the understanding of others.</p>

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.)--Cornell University, January, 2007. / Vita. Includes bibliographical references (leaves 107-130).

Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 138-148). Also available on the Internet.

Thesis (M. Sc.)--University of Canterbury, 2008. / Typescript (photocopy). Includes bibliographical references (leaves 76-93). Also available via the World Wide Web.

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / "August 2000." Typescript. Vita. Includes bibliographical references (leaves 189-210). Also available on the Internet.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.