Thesis (M.S.)--University of Toledo, 2008. / "In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 44-53, p. 77-90.

Thesis (Ph. D.)--Drexel University, 2004. / Includes abstract and vita. Includes bibliographical references (leaves 113-130).

Thesis (Ph.D.)--University of Florida, 2005. / Typescript. Title from title page of source document. Document formatted into pages; contains 124 pages. Includes Vita. Includes bibliographical references.

One of the most common risk factors for stroke is diabetes. Diabetics are 2 to 4 times more likely to have a stroke and are also significantly more likely to show poor functional recovery. In order to determine why diabetes is associated with poor stroke recovery, we tested the hypotheses that diabetes either exacerbates initial stroke damage, or inhibits neuronal circuit plasticity in surviving brain regions that is crucial for successful recovery. Type 1 diabetes was chemically induced in mice four weeks before receiving a targeted photothrombotic stroke in the right forelimb somatosensory cortex to model a chronic diabetic condition. Following stroke, a subset of diabetic mice were treated with insulin to determine if controlling blood glucose levels could improve stroke recovery. Consistent with previous studies, one behavioural test revealed a progressive improvement in sensory function of the forepaw in non-diabetic mice after stroke. By contrast, diabetic mice treated with and without insulin showed persistent deficits in sensori-motor forepaw function. To determine whether these different patterns of stroke recovery correlated with changes in functional brain activation, forepaw evoked responses in the somatosensory cortex were imaged using voltage sensitive dyes at 1 and 14 weeks after stroke. In both diabetic and non-diabetic mice that did not have a stroke, brief mechanical stimulation of the forepaw evoked a robust and near simultaneous depolarization in the primary (FLS1) and secondary somatosensory (FLS2) cortex. One week after stroke, forepaw-evoked responses had not been remapped in the peri-infarct cortex in both diabetic and non-diabetic mice. Fourteen weeks after stroke, forepaw evoked responses in non-diabetic mice re-emerged in the peri-infarct cortex whereas diabetic mice showed very little activation, reminiscent of the 1 week recovery group. Moreover, controlling hyperglycemia using insulin therapy failed to restore sensory evoked responses in the peri-infarct cortex. In addition to these differences in peri-infarct responsiveness, we discovered that stroke was associated with increased responsiveness in FLS2 of non-diabetic, but not diabetic or insulin treated mice. To determine the importance of FLS2 in stroke recovery, we silenced the FLS2 cortex and found that it re-instated behavioural impairments in stroke recovered mice, significantly more so than naïve mice that still had a functioning FLS1. Collectively, these results indicate that both diabetes and the secondary somatosensory cortex play an important role in determining the extent of functional recovery after ischemic cortical stroke. Furthermore, the fact that insulin therapy after stroke did not normalize functional recovery, suggests that prolonged hyperglycemia (before stroke) may induce pathological changes in the brain’s circulation or nervous system that cannot be easily reversed. / Graduate

The Postcentral gyrus of the brain of the cat has been studied with the technics of Nisel and Golgi. Qualitative data concerning packing densities and volumes of the nerve cells and of the glia, as welll as the distribution of the dendrites are reported. The existence of alternate dendritic and axonal layers has been demonstrated and the relationship of these layers to the stripes of Baillarger has been analyzed. / fr

abstract: In the past decade, research on the motor control side of neuroprosthetics has steadily gained momentum. However, modern research in prosthetic development supplements a focus on motor control with a concentration on sensory feedback. Simulating sensation is a central issue because without sensory capabilities, the sophistication of the most advanced motor control system fails to reach its full potential. This research is an effort toward the development of sensory feedback specifically for neuroprosthetic hands. The present aim of this work is to understand the processing and representation of cutaneous sensation by evaluating performance and neural activity in somatosensory cortex (SI) during a grasp task. A non-human primate (Macaca mulatta) was trained to reach out and grasp textured instrumented objects with a precision grip. Two different textures for the objects were used, 100% cotton cloth and 60-grade sandpaper, and the target object was presented at two different orientations. Of the 167 cells that were isolated for this experiment, only 42 were recorded while the subject executed a few blocks of successful trials for both textures. These latter cells were used in this study's statistical analysis. Of these, 37 units (88%) exhibited statistically significant task related activity. Twenty-two units (52%) exhibited statistically significant tuning to texture, and 16 units (38%) exhibited statistically significant tuning to posture. Ten of the cells (24%) exhibited statistically significant tuning to both texture and posture. These data suggest that single units in somatosensory cortex can encode multiple phenomena such as texture and posture. However, if this information is to be used to provide sensory feedback for a prosthesis, scientists must learn to further parse cortical activity to discover how to induce specific modalities of sensation. Future experiments should therefore be developed that probe more variables and that more systematically and comprehensively scan somatosensory cortex. This will allow researchers to seek out the existence or non-existence of cortical pockets reserved for certain modalities of sensation, which will be valuable in learning how to later provide appropriate sensory feedback for a prosthesis through cortical stimulation. / Dissertation/Thesis / M.S. Bioengineering 2011

Primary sensory cortex has long been believed to play a straightforward role in the initial processing of sensory information. Yet, the superficial layers of cortex overall are sparsely active, even during strong sensory stimulation; moreover, cortical activity is influenced by other modalities, task context, reward, and behavioral state. The experiments described in this thesis demonstrate that reinforcement learning dramatically alters representations among longitudinally imaged neurons in superficial layers of mouse primary somatosensory cortex. Cells were confirmed to be sparsely active in naïve animals; however, learning an object detection task recruited previously unresponsive neurons, enlarging the neuronal population sensitive to tactile stimuli. In contrast, cortical responses habituated, decreasing upon repeated exposure to unrewarded stimuli. In addition, after conditioning, the cell population as well as individual neurons better encoded the rewarded stimuli, as well as behavioral choice. Furthermore, in well-trained mice, the neuronal population encoded of the passage of time. We further found evidence that the temporal information was contained in sequences of cell activity, meaning that different cells in the population activated at different moments within the trial. This kind of time-keeping was not observed in naïve animals, nor did it arise after repeated stimulus exposure. Finally, unexpected deviations in trial timing elicited even stronger responses than touch did. In conclusion, the superficial layers of sensory cortex exhibit a high degree of learning-dependent plasticity and are strongly modulated by non-sensory but behaviorally-relevant features, such as timing and surprise.

No description available.

Merging the senses is key to perception, yet how we achieve this remains unclear. New research finds multimodality even in primary sensory areas, but its role is not understood. We address this question by using in vivo 2-photon calcium imaging in awake mice to test several hypotheses about the possible functions primary somatosensory cortex (S1) may subserve in integrating auditory and tactile sensory input. We first test whether S1 encodes pure auditory stimulus identity by training a linear classifier to decode different sounds from S1 activity. We find that decoder accuracy is slightly-but-significantly above chance, suggesting that S1 weakly encodes sounds. We then ask whether S1 encodes specific audio-tactile feature conjunctions by testing decoder performance for distinct combinations of simultaneously-presented auditory and tactile stimuli. We find that accuracy was within chance levels, indicating that sound-evoked suppression of whisker responses is auditory-stimulus non-specific. Subsequently, we test whether passive experience is sufficient to induce either a) Hebbian-like reactivation of tactile stimulus representations by correlated auditory stimuli or b) enhanced mixed selectivity. We find that passive experience results in neither effect. We also find S1’s auditory and audio-tactile encoding properties to be stable in the face of reinforcement conditioning. As part of a separate project, we also present results that reinforcement conditioning enhances encoding of time and temporal surprise in primary somatosensory cortex.

Neocortical sensory areas have associated primary and secondary thalamic nuclei. While primary nuclei transmit sensory information to cortex, secondary nuclei remain poorly understood. I recorded juxtasomally from the secondary somatosensory (POm) and visual (LP) nuclei of awake mice. POm activity correlated with whisking, but not precise whisker kinematics. This movement modulation was not a result of sensory reafference, nor was it due to input from motor or somatosensory cortex, nor the superior colliculus. Whisking and pupil dilation were strongly correlated, reflecting arousal. Indeed LP, which is not part of the whisker system, tracked whisking equally well, indicating that POm activity does not encode whisker movement per se. The semblance of movement-related activity is likely instead a global effect of arousal on both nuclei. I then investigated how POm and LP may support feature-based attention. I trained head-fixed mice to attend to one sensory modality while ignoring a second modality. I used multielectrode arrays to record simultaneously from both regions. In mice trained to respond to tactile stimuli and ignore visual stimuli, POm was robustly activated by touch and largely unresponsive to visual stimuli. The reverse pattern was observed when mice were trained to respond to visual stimuli and ignore touch, with POm now more robustly activated during visual trials. This POm activity was not explained by differences in movements (i.e., whisking, licking) resulting from the two tasks. LP exhibited similar phenomena. I conclude that behavioral training reshapes activity in secondary thalamic nuclei. Secondary nuclei may respond to behaviorally relevant, reward-predicting stimuli regardless of stimulus modality.