Pro-opiomelanocortin (POMC) is the precursor of many neuropeptides which includ adrenocorticotropin (ACTH). ACTH has a biological activity in regulating adrenocortical function. In the present study, we will investigate the effect of POMC gene transfer on adrenal cortex cells in cell cultures and animal models. The study included adrenal cortical H295R cells for adenovirus-mediated gene delivery. The effects of POMC gene on H295R cell steroidogenesis and cell proliferation were investigated. In addition, there were 32 SD rats dividing into three groups. 1) Control, injected with normal saline via tail vein (n = 8); 2) Ad-GFP, injected with adenovirus containing GFP (n=12); 3) Ad-POMC, injected with adenovirus containing recombinant POMC gene (n=12). Body weight (BW) was measured. Adrenals were collected, fixed and a series of sections were cut for stains for PCNA and MC2-R. The plasma cortisol and VEGF levels of rats were measured. The results showed that Ad-POMC delivery significantly increased the ACTH and cortisol levels by 50-100 fold and 20-100% in H295R cells, respectively. In addition, Ad-POMC delivery significantly inhibited the cell proliferation and increased the apoptotic cells. The expression of MC2-R protein of H295R cells was also suppressed after Ad-POMC delivery. In the study of SD rats, the Ad-POMC-treated rats exhibited reduced weight gain compared with other groups in the first 2 weeks; however, there was no significant change in BW between Ad-POMC and Ad-GFP groups during the experimental period. The weight of adrenal in Ad-POMC-treated rats was significantly higher than Ad-GFP group in the 8th week. Comparing the sequential adrenal weights in Ad-POMC group, those in 6th week were significantly higher than in 2nd and 4th weeks. The plasma VEFG levels of Ad-POMC-treated rats were higher than Ad-GFP group in the 8th week. The adrenal sections showed that Ad-POMC treated rats had moreanti-PCNA stained cells than Ad-GFP treated rats in 8th week. However, less anti-MC2R stained cells were found in Ad-POMC treated rats in 8th week. Ad-POMC treated rats had higher plasma cortisol levels than those in Ad-GFP treated rats, however, there were no statistical significances. In conclusion, POMC gene transfer modulates the morphology and function of the adrenal cortex. POMC gene inhibits the H295R cells proliferation by inducing MC2-R down-regulation and cells apoptosis. In SD rat adrenal, however, it stimulates adrenal cortex in biphasic pattern. The rapid growing pattern noted in the later phase may be due to the effect of VEGF. Besides, the physical regulation of cortisol synthesis is much stricter than that of ACTH.

The overall goals of this dissertation were 1) to understand the role that neurons in primate primary visual cortex (V1) play in the detection of small visual stimuli, and 2) to understand the quantitative relationship between the responses of individual neurons and neural population responses in V1. These goals were addressed in experiments with awake, behaving macaque monkeys using electrophysiological and imaging techniques. Initially, I employed ideal observer models to assess V1 neural detection sensitivity in a reaction-time visual detection task and found it to be comparable to the monkey's detection sensitivity. Using the same detection task, I found weak, but significant, correlations between V1 neural activity and the trial-by-trial behavior of monkeys (choice and reaction time). The conclusion of these studies is that the monkey's behavior in the detection task was likely mediated by large neural populations. Voltage-sensitive dye imaging (VSDI) is a powerful imaging technique that is well suited for assessing the link between the activity of large neural populations and behavior. VSDI measures changes in membrane potential over a cortical area of 1-2 cm² with high spatial and temporal resolutions. Using position tuning experiments with VSDI and electrophysiology, I described the relatively unknown quantitative relationships between spiking activity, the local field potential, and VSDI. These relationships were well captured by non-linear transfer functions. Lastly, these experiments also revealed important new findings about the representation of visual space by populations of neurons in V1. In particular, we resolved a long standing debate regarding the size of the cortical point image (CPI), the area of cortex activated by a single point stimulus. We found that the CPI is constant across eccentricity in parafoveal V1, suggesting that each point in space activates an approximately equivalent amount of cortical tissue. In conclusion, the results and analyses described in this dissertation contribute to our understanding of the role that neural populations in V1 play in mediating visual detection, reveal important properties of the representation of visual space by populations of neurons in V1, and provide the first analysis of the quantitative relationship between VSDI and electrophysiological signals. / text

Previous studies have shown that analogy instruction can be applied effectively in science education and motor skill acquisition; however, little is known about the application of analogy in speech motor performance. In four experiments, analogy instructions were tested in the speech domain. The first experiment (Chapter 2) used focus group methodology to establish a set of analogies that related pitch variation during speech production to a ‘waves at sea’ metaphor. The analogies were then used to elicit speech with different pitch variations. Analogy instructions were more effective than explicit instructions for eliciting speech with minimum pitch variation (i.e., monotonous speech). In the second experiment (Chapter 3), the influence of both analogy and explicit instructions on the perception of speech parameters invoked by maximum pitch variation was examined. Pitch variation in analogy instructed speech was perceived to be greater and more natural than when explicit instructions were provided. In the third experiment (Chapter 4), stress resistance in analogy instructed speech performance was evaluated. Analogy instructed speech performance was demonstrated to be significantly more stable under a psychologically stressful condition than explicitly instructed speech. The last experiment (Chapter 5), investigated the cognitive load of analogy on different components of the working memory system during speech performance. It was found that analogy instructions tended to place more cognitive load on the visual component of working memory than explicit instructions. The findings of the four experiments inform the application of analogy in speech motor skill performance in general, and contribute to understanding the mechanisms that underpin analogy within a working memory framework. The work also has significant potential for application in speech-language pathology treatment. / published_or_final_version / Human Performance / Doctoral / Doctor of Philosophy

Our sensory experiences are encoded in the patterns of activity of the neurons in our brain. While we know we are capable of sensing and responding to a constantly changing sensory environment, we often study neural activity by repeatedly presenting the same stimulus and analyzing the average neural response. It is not understood how the average neural response represents the dynamic neural activity that produces our perceptions. In this work, we use functional imaging of the rodent primary somatosensory cortex, specifically the whisker representations, and apply classic signal-detection methods to test the predictive power of the average neural response. Stimulus features such as intensity are thought to be perceptually separable from the average representation; however, we show that stimulus intensity cannot be reliably decoded from neural activity from only a single experience. Instead, stimulus intensity was encoded only across many experiences. We observed this probabilistic neural code in multiple classic sensory paradigms including complex temporal stimuli (pairs of whisker deflections) and multi-whisker stimuli. These data suggest a novel framework for the encoding of stimulus features in the presence of high-neural variability. Specifically we suggest that our brains can compensate for unreliability by encoding information redundantly across cortical space. This thesis predicts that a somatosensory stimulus is not encoded identically each time it is experienced; instead, our brains use multiple redundant pathways to create a reliable sensory percept.

No description available.

Synaptic plasticity reflects the capacity of synapses to undergo changes in synaptic strength and connectivity, and is highly regulated by age and sensory experience. This thesis focuses on the characterization of synaptic plasticity in the primary auditory cortex (A1) of rats throughout development and following sensory deprivation. Initial experiments revealed an age-dependent decline in plasticity, as indicated by reductions in long-term potentiation (LTP). The enhanced plasticity of juvenile rats appeared to be mediated by NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR), as NR2B antagonist application reduced LTP to adult-like levels in juveniles, yet had no effect in adults. The importance of sensory experience in mediating plasticity was revealed in experiments using white noise exposure, which is a sensory deprivation technique known to arrest cortical development in A1. Notably, adult rats reared in continuous white noise maintained more juvenile-like levels of LTP, which normalized upon subsequent exposure to an unaltered acoustic environment. The white noise-induced LTP enhancements also appeared to be mediated by NR2B subunits, as NR2B antagonists reversed these LTP enhancements in white noise-reared rats. Given the strong influence that sensory experience exerts on plasticity, additional experiments examined the effect of shorter episodes of white noise exposure on LTP in adult rats. Exposure to white noise during early postnatal life appeared to “prime” A1 for subsequent exposure in adulthood, resulting in enhanced LTP. The necessity of early-life exposure was evident, as repeated episodes of white noise in adulthood did not enhance plasticity. In older rats that typically no longer express LTP in A1, pharmacological methods to enhance plasticity were explored. Moderate LTP was observed in older rats with cortical zinc application, which may act through its antagonism of NR2A subunits of the NMDAR. Additionally, current source density and cortical silencing analyses were conducted to characterize the distinct peaks of field postsynaptic potentials recorded in A1, with the earlier and later peaks likely representing thalamocortical and intracortical synapses, respectively. Together, this thesis emphasizes the critical role of sensory experience in determining levels of cortical plasticity, and demonstrates strategies to enhance plasticity in the mature auditory cortex. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2011-01-11 14:53:57.677

Music depends on the perception and production of complex temporal patterns, or rhythms, as a vital part of its power to communicate. These experiments investigated the neuroanatomical substrate of rhythm perception and production in patients with focal cerebral lesions, and in neuroimaging studies with normals. The hypotheses focused on the role of the primary and secondary auditory cortex, as well as the cerebellum and other motor-related areas. / Experiment I. To estimate the extent of removals in the region of auditory cortex in neurosurgical patients, a 3D probabilistic map of Heschl's gyrus (HG) was developed from magnetic resonance imaging (NW scans of normals. The map was coregistered with patent MRIs, revealing that most removals involved only anterior secondary auditory cortical regions, with relatively little encroachment onto primary auditory cortex. Additionally, this experiment compared the volumes of HG between hemispheres and found a consistent L > R asymmetry in the volume of cortical white matter, which could contribute directly to the preferential left-hemisphere processing of speech. / Experiment II. Using a paradigm contrasting reproduction of auditory and visual rhythms, four groups of patients were tested: those with right or left anterior temporal-lobe removals (RT-a, LT-a) and those with similar removals which also included HG (RT-A, LT-A). RT-A patients were impaired on auditory but not visual rhythms, particularly when accurate reproduction of stimulus durations was required. In contrast, LT-a, RT-a and LT-a patients were not impaired. These results demonstrated a role for the right anterior secondary auditory cortical regions in the retention of auditory temporal information. / Experiment III. The rhythm reproduction paradigm was adapted for a positron emission tomography (PET) activation study in normals. These data confirmed the participation of secondary auditory regions in the retention of auditory temporal information. They also demonstrated a supra-modal contribution of the lateral cerebellar cortices, vermis and basal ganglia to the task, pointing to a distributed system of neural structures involved in the production of a timed motor response from external stimuli. / The results are discussed in relation to possible interhemispheric differences in auditory temporal processing as well as the role of the cerebellum in motor and perceptual timing.

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by increased hyperactivity, impulsivity, and inattention. Some theories propose that ADHD is caused by a deficit in inhibitory control, interacting with other executive functions (e.g., emotional control) to lead to behavioural dysfunction. Furthermore, certain brain regions have been found to be involved in executive functions, and several studies have examined the neural correlates of ADHD at broad-based levels. Increased interest has been placed on the Anterior Cingulate Cortex (ACC), which is known to play a role in attention and other complex cognitive processes. Thus, to further clarify the nature of the behavioural and cognitive deficits observed in ADHD, and to elucidate potential relationships between these difficulties and their neural substrates with more specificity, volumetric analyses of the ACC were conducted. For this purpose, 10 children with ADHD and 10 matched controls underwent magnetic resonance imaging and neuropsychological assessment. Manual tracing of ACC subregions was conducted using ANALYZE 9.0 (Mayo Clinic), followed by between-group statistical comparisons. Correlation analyses were used to investigate whether ACC subregions were associated with performance on executive functions tasks. It was hypothesized that there would be significant volumetric groups differences between the two groups, and that subregions would have a differential relationship with executive function performance. Results indicated the ADHD group has marginally larger right dorsal ACC volumes relative to controls. Further, between the two groups, brain-behaviour relationships were different. These results provide support for the hypothesis of a delay in neuronal maturation of the ACC in children with ADHD from Spain. / Graduate

No description available.

The mammalian visual cortex is believed to be parcellated into functional radial units called modules, which are composed of neurons with similar physiological properties. The first demonstration of modularity was provided in 1957 by Mountcastle in the somatosensory cortex, and has since been demonstrated in the visual cortex, where neurons within a vertical unit of the visual cortex process information about the same portion of the visual field. / A new approach has been proposed for identifying functionally similar neurons by examining their molecular characteristics. Indeed, the arrangement of neurons into functional arrays might be reflected by the presence of specific molecules (e.g Cat-301 patches, cytochrome oxidase blobs). / In this experiment, immunohistochemistry was used to examine the tangential and radial distribution and development of a subset of pyramidal neurons in the kitten and adult cat visual cortex using the monoclonal antibody SMI-32, that recognizes the non-phosphorylated form of neurofilament H. It was found that the neurons recognized by this antibody were grouped into clusters, forming regularly spaced patches in the infragranular and supragranular layers. These anatomical findings support the notion of an intrinsic columnar organization.