No description available.

No description available.

No description available.

The pattern and complexity of cerebellar folding varies across vertebrates. However, little is known about how the tissue-level mechanics are adjusted to create species-specific folding patterns. Here, we utilize a variety of species with differences in cerebellar folding amount to investigate two tissue-level mechanics known to affect folding—differential expansion and outer layer thickness. We found that the level of differential expansion between the outer and inner layers of the cerebellum broadly correlates with folding amount and that the thickness of the outer layer is important as thicker outer layers require more differential expansion to fold. Additionally, we find that both the proliferation rate and division angle of cells in the outer layer are adjusting these two mechanics. This work will shed light on the conservation of the tissue mechanics that regulate brain folding and how these mechanics may be modulated to set the diverse folded morphologies observed across species.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Thesis (Ph.D.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Centre for Neuroscience. Title from pdf file main screen (viewed on August 25, 2009). Includes bibliographical references.

Call number: LD2668 .T4 1984 B423 / Master of Science / Diagnostic Medicine/Pathobiology

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Learning and memory has been a topic that has captured the attention of the scientific and public communities since the dawn of scientific discovery. Without the faculty of memory, mammals cannot experience nor function in the world; among homosapiens specifically, language, relationships, and personal identity cannot be developed (Eysenck, 2012). After all, some philosophers such as John Locke argued we are nothing but a collection of past memories in which we have developed and improved upon (Nimbalkar, 2011). Understanding the cellular mechanisms behind learning, and the subsequent formation of memory, has been a topic that has garnered scientific interest for many decades. One particular kinase that has been at the center of attention in the last decade is the serine/threonine kinase PKM-ζ, an N-terminal truncated form of PKC-ζ that renders it constitutively active (Hernandez et al., 2003). PKM-ζ has long been implicated in a cellular correlate of learning, long-term potentiation (LTP). Inhibition of PKM-ζ with Zeta-inhibitory peptide (ZIP) has been shown in many brain structures to disrupt maintenance of AMPA receptors, irreversibly disrupting numerous forms of learning and memory that have been maintained for weeks. The voltage-gated potassium channel Kv1.2 is a critical modulator of neuronal physiology, including dendritic excitability, action potential propagation, and neurotransmitter release. While expressed in various mammalian tissues, Kv1.2 is most prevalent in the cerebellum where it modulates both dendritic excitability of Purkinje cells (PCs) and basket cell (BC) inhibitory input to PCs. Because PCs are the main computational unit of the cerebellar cortex and provide its sole output (Napper et al., 1988; Harvey et al., 1991), regulation of synaptic Kv1.2 is predicted to have a major role in cerebellar function. Pharmacological inhibition of Kv1.2 in cerebellar PC dendrites increases excitability (Khavandgar et al., 2005), while its inhibition in BC axon terminals increases inhibition to PCs (Southan & Robertson, 1998). Interestingly, two prior studies have demonstrated that PKC-ζ, an atypical Protein Kinase C, is able to phosphorylate and bind cerebellar Kvβ2, a Kv1.2 auxiliary subunit. (Gong et al., 1999; Croci et al., 2003). Delay eyeblink conditioning (EBC) is an established model for the assessment of cerebellar learning. Despite being highly expressed in the cerebellum, no studies have examined how regulation of cerebellar PKM-ζ may affect cerebellar-dependent learning and memory nor have they examined the possible effect PKM-ζ may have on Kv1.2. The goal of this dissertation was to determine whether PKM-ζ could modulate EBC in a Kv1.2 dependent manner. Through the use of microscopy techniques we have shown that PKM-ζ is highly expressed in the cerebellar cortex, primarily in the PC, and by the use of pharmacological manipulations, it was found that PKM-ζ has an important role in regulating the acquisition of EBC. Through the use of biotinylation, flow cytometry, and behavioral manipulations, it was determined that PKM-ζ regulates Kv1.2 during eyeblink conditioning. These studies provided the first evidence that PKM-ζ has a role for learning and memory in the cerebellum, and the first evidence of PKM-ζ regulating a voltage-gated ion channel rather than a ligand-gated ion channel such as AMPA receptors.

The ability of the brain to change structurally and functionally with experience is called brain plasticity. High levels of pro-inflammatory cytokines impair normal memory formation and consolidation. To better understand the role of pro-inflammatory cytokines in learning, the contribution of the cytokine interleukin-6 (IL-6) to a motor skill learning task investigated. The Fmr1 Knockout (KO) mouse, an animal model of Fragile X Syndrome, has demonstrated impaired neural plasticity and learning. Fmr1 KO and control wild-type (WT) mice were trained on the dowel and flat beam runways to study motor skill learning and motor activity respectively. The cerebellum from the animals was examined for IL-6 protein using ELISA. No significant differences in the levels of IL-6 in the cerebellum of the Fmr1 KO and WT normal mice were found. The expression of IL-6 was not altered by the behavioural training. These results suggest lack of association between IL-6, and FMRP and motor skill learning. / October 2016