Murine models have become increasingly popular to study various aspects of cardiovascular diseases due to their ease of genetic manipulation. Unfortunately, there has been little effort put into describing the distribution of autonomic nerves in the mouse heart, making it difficult to compare current findings from clinical and experimental models related to cardiovascular diseases. Furthermore, determination of the requirements for the development of this system and its maintenance in adult mice remains largely unexplored. This study represents the first detailed mapping of cholinergic neuroanatomy of the mouse heart based on immunohistochemical staining using true cholinergic markers. We found cholinergic innervation of the mouse heart to be largely focused in the atrium and conducting system. We investigated the involvement of the neurotrophic factor neurturin (NRTN) in the development of cholinergic innervation, because there was indirect evidence that implicated it as a crucial factor. Results from our work definitively demonstrate that NRTN plays a major role in the development of cardiac parasympathetic ganglia and cholinergic innervation of the mouse heart. Adult NRTN knockout mice exhibited a drastic reduction in the number of intracardiac neurons with decreased atrial acetylcholine, cholinergic nerve density at the sinoatrial node and negative chronotropic responses to vagal stimulation. The presence of NRTN and its receptors in hearts from adult wild-type mice suggests that this neurotrophic factor might also be required for maintenance of cardiac cholinergic innervation. Finally, we wanted to determine how intracardiac neurons and their processes change during diseased states, specifically type 1 diabetes. This work has shown that the cardiac cholinergic nervous system in the mouse undergoes structural and functional remodeling when challenged with streptozotocin-induced diabetes. Cholinergic nerves in diabetic hearts undergo extensive sprouting at the sinoatrial node with no change in the number of intracardiac neurons. Cholinergic function appears to be enhanced in diabetic mice, based on pharmacological testing, despite decreased response to direct vagal nerve stimulation. Evidence also suggests that diabetic mice have an imbalance in autonomic control of heart rate. The latter findings suggest that disruption of central input into intrinsic cardiac ganglia also contributes to the neuropathology of type 1 diabetes.

The ophthalmic trigeminal placode (opV) is the birth place of one cell type of sensory neurons contributing to the trigeminal ganglion. Signals from the neural tube induce placodal identity within the surface ectoderm. Specified opV placode cells then up-regulate neuron differentiation markers and migrate to the ganglion. Several molecular pathways have been shown to act in opV placode cell development. Despite this, signals that specify individual neurons from within the opV placode remain unknown. However, it is known that components of the Notch signaling pathway are expressed in the opV placode. I tested the role of Notch signaling in opV placode development by separately inhibiting and over-activating the pathway. Using DAPT, an inhibitor of gamma-secretase, I inhibited Notch signaling in 13-15 somite stage chick embryo heads. Attenuated Notch signaling caused increased neuronal differentiation of opV cells at 13-15 somites. I also observed an increase in migratory opV placode (Pax3+) cells in the mesenchyme and expression of neuronal marker Islet1 in the ectoderm. Further, I activated Notch signaling by misexpressing the Notch intracellular domain (NICD) by in ovo electroporation of 10-12 somite stage chick embryos. This resulted in Pax3+ targeted cells failing to differentiate and remain instead in the ectoderm. Thus, Notch/Delta signaling plays an important role in selecting ophthalmic trigeminal cells to differentiate and migrate to the trigeminal ganglion.

Machine learning is a field that is inspired by how humans and, by extension, the brain learns.The brain consists of a biological neural network that has neurons that are either active or inactive. Modern-day artificial intelligence is loosely based on how biological neural networks function. This paper investigates whether a multi layered perceptron that utilizes inactive/active neurons can reduce the number of active neurons during the forward and backward pass while maintaining accuracy. This is done by implementing a multi layer perceptron using a python environment and building a neuron activation algorithm on top of it. Results show that it ispossible to reduce the number of active neurons by around 30% with a negligible impact on test accuracy. Future works include algorithmic improvements and further testing if it is possible to reduce the total amount of mathematical operations in other neural network architectures with a bigger computational overhead.

No description available.

A well documented laboratory setup, leech preparation process, and bio-potential data recording process are needed. Repeatability and quality data recordings are essential and thus dictate the requirements of the laboratory setup and processes listed above. Advances in technology have both helped and hindered this development. While very precise equipment is required to record the low voltage bio-potentials, noisy electronic equipment and wires surrounding the work area provide high levels of interference. Proper laboratory setup and data recording processes, however, limit the unwanted interference. Quality data can only be recorded from a properly handled and prepared leech subject. Proper setup and procedures result in quality recordings which lend a clean signal for furthering the understanding of nerve functionality. The electrophysiology lab at California Polytechnic State University in San Luis Obispo is an example of a proven lab setup for high quality signal capture.

A neutron activation analysis procedure for the simultaneous determination of Au, Pd and Ir, and separate determination of Os is described and applied to the determination of these metals in the Mount Albert ultramafic pluton, Quebec. The Mount Albert is an alpine-type ultramafic body whose petrography, geology and geochemistry has been discussed in some detail by MacGregor (1962, 1964). It consists mainly of serpentinized dunite and peridotite. However, it is distinguished by the presence of an eastern lobe which is essentially unserpentinized. In addition to ferromagnesians, two varieties of spinel including disseminated accessory chrome spinel and massive, discordant chromite veins or schlieren are important mineralogical constituents. Twenty samples were analyzed including 5 fresh dunites and peridotites, 8 serpentinized equivalents, 4 disseminated chrome spinels, 1 clinopyroxenite, and 2 massive chromite. The concentrations (in p. p. b.) of average fresh ultramafics and their serpentinized equivalents are:-------------------------------------- ---------------------Pd----Os----Ir----Au------------------------------------------- Fresh rocks------------7.7----7.2--2.5--0.99------------------------------------------- Serpentinized rocks---10----6.6--2.2---2.4-------------------------------------------- The piuton was intruded as a nearly solid mass of olivine and some orthopyroxene with about 15 weight per cent melt. A small concentration of the precious metals, a factor of 2 to 3, in the melt relative to crystalline phases appears to have occurred. The disseminated chrome spinel and massive chromite appear to concentrate the precious metals. In particular, Os and Ir content of the massive chromite is approximately 10 times that of fresh or serpentinized whole rocks. There is little change in average precious metal content with serpentinization. Pd shows a slight increase, and Ir and Os slight decreases in concentration with degree of serpentinization. Only Au appears significant to be enriched in serpentinized rocks where a twofold increase occurs. The variation in precious metal content of all four metals increase when the rocks are serpentinized: When normalized to chondrite meteorites, the precious metal data give fractionation trends similar to that of average chondrite. These trends are compatible with a model in which alpine ultramafics are regarded as residua from the partial melting of parental material of approximately chondritic composition. / Thesis / Master of Science (MSc)

Mammals are born on a precocial–altricial continuum. Altricial species produce helpless neonates with closed distant organs incapable of locomotion, whereas precocial species give birth to well-developed young that possess sophisticated sensory and locomotor capabilities. Previous studies suggest that distinct patterns of cortex development differ between precocial and altricial species. This study compares patterns of neocortex neurogenesis and maturation in the precocial guinea pig and altricial dwarf rabbit, both belonging to the taxon of Glires. We show that the principal order of neurodevelopmental events is preserved in the neocortex of both species. Moreover, we show that neurogenesis starts at a later postconceptional day and takes longer in absolute gestational days in the precocial than the altricial neocortex. Intriguingly, our data indicate that the dwarf rabbit neocortex contains a higher abundance of highly proliferative basal progenitors than the guinea pig, which might underlie its higher encephalization quotient, demonstrating that the amount of neuron production is determined by complex regulation of multiple factors. Furthermore, we show that the guinea pig neocortex exhibits a higher maturation status at birth, thus providing evidence for the notions that precocial species might have acquired the morphological machinery required to attain their high functional state at birth and that brain expansion in the precocial newborn is mainly due to prenatally initiating processes of gliogenesis and neuron differentiation instead of increased neurogenesis. Together, this study reveals important insights into the timing and cellular differences that regulate mammalian brain growth and maturation and provides a better understanding of the evolution of mammalian altriciality and presocialit

Mammals are born on a precocial–altricial continuum. Altricial species produce helpless neonates with closed distant organs incapable of locomotion, whereas precocial species give birth to well-developed young that possess sophisticated sensory and locomotor capabilities. Previous studies suggest that distinct patterns of cortex development differ between precocial and altricial species. This study compares patterns of neocortex neurogenesis and maturation in the precocial guinea pig and altricial dwarf rabbit, both belonging to the taxon of Glires. We show that the principal order of neurodevelopmental events is preserved in the neocortex of both species. Moreover, we show that neurogenesis starts at a later postconceptional day and takes longer in absolute gestational days in the precocial than the altricial neocortex. Intriguingly, our data indicate that the dwarf rabbit neocortex contains a higher abundance of highly proliferative basal progenitors than the guinea pig, which might underlie its higher encephalization quotient, demonstrating that the amount of neuron production is determined by complex regulation of multiple factors. Furthermore, we show that the guinea pig neocortex exhibits a higher maturation status at birth, thus providing evidence for the notions that precocial species might have acquired the morphological machinery required to attain their high functional state at birth and that brain expansion in the precocial newborn is mainly due to prenatally initiating processes of gliogenesis and neuron differentiation instead of increased neurogenesis. Together, this study reveals important insights into the timing and cellular differences that regulate mammalian brain growth and maturation and provides a better understanding of the evolution of mammalian altriciality and presociality.

No description available.

No description available.