Slow Gamma Takes the Reins in Replay

The mechanisms supporting hippocampal memory reactivation are puzzling. Reactivation occurs during ripple oscillations, yet ripples are not coordinated across regions. In this issue of Neuron, Carr et al. (2012) report that another oscillation, slow gamma, coordinates memory reactivation across the hippocampal network

Alternative perceptions of reality: dyslexia

My MVA work, Alternative Perceptions of Reality: Dyslexia, revolves around dyslexia and ways in which dyslexic artists, like myself, represent reality in their art. I focus on how dyslexics perceive space and time, how this is represented in their work and how it manifests in my own work. The introduction describes why dyslexia is relevant to art, provides more detail on dyslexia itself and ways dyslexia can affect perception. Surrealism and Symbolism are discussed in order to draw parallels with dyslexic perception. Chapter 1 describes the influences on my own work, including dyslexia, primitive art and symbolism. The second chapter profiles two well known artists with dyslexia: Robert Rauschenberg and Pablo Picasso. I examine ways in which they represent space or reality and how dyslexic perception is apparent in their works. Similarly, in Chapter 3, I discuss the works of the contemporary dyslexic artists Terry A. Orchard and Katharine Dowson, including the results of interviews and surveys I conducted. Throughout this dissertation, I also discuss my own experience of dyslexia and how it is expressed through my paintings. In the conclusion, I discuss what I have learned about the work of myself and other dyslexic artists: How our paintings are a glimpse of alternative inner realities

Synthetic Approaches to Novel Pyridine and Indole Derivatives as Potential Agents for the Treatment of Neurodegenerative Disorders

Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Lewy Body Disease (LBD) are some of the many neurodegenerative disorders associated with dementia, for which there is no ultimate cure. It is widely accepted that central nervous system (CNS) nicotinic acetylcholine receptors (nAChRs) may be strongly implicated in the pathology of these devastating disorders, and that stimulation of nAChRs can enhance cognitive behaviour in animals and humans. Nicotine and other nicotinic receptor binding compounds have, over many years, been explored as potential therapies for disorders such as AD and PD. This thesis describes the preparation and pharmacological investigation of a series of 3- substituted and 3,5-disubstitued pyridine derivatives as potential novel and selective nictotinic receptor agonists. Chapter Two details the synthesis of targeted compounds using the generation of [(pyridin-3-yl)methyl]lithium and [(5-methylpyridin-3- yl)methyl]lithium, respectively and subsequent reaction with various electrophiles. Unsuccessful attempts at the synthesis of enantiomerically pure 4-substituted arylpyridin-3-yl-ethanol derivatives by reduction of prochiral 4-substituted arylpyridin-3-yl-ethanone derivatives were made using both catalytic and enzymatic approaches; however, a pair of enantiomerically pure alcohols were isolated via the resolution of diastereomeric esters (prepared by reaction with (S)-O-acetyl mandelic acid) and subsequent hydrolysis. iv Chapter Three explores the synthesis of targeted compounds using halogen-lithium exchange reactions of 3-bromopyridine using n-BuLi and ring-opening by the resultant pyridin-3-yllithium of 4-substituted aryl epoxides. As an extension, Sonogashira cross-coupling of 3- bromopyridine and 4-substituted arylacetylenes and subsequent hydration as an approach to 4-substituted pyridin-3-yl-ethanone derivatives is described. A series of indole derivatives were synthesised using identical approaches. Using methodology developed in previous Chapters, Chapter Four describes approaches to symmetrical and asymmetrical 3,5- bis(arylethynyl)pyridine derivatives, the corresponding bis(ketones), alcohols and 3,5-disubstituted keto-alcohol products. Chapter Five details preliminary pharmacological data (binding and functional assays) performed by our collaborators at Institut de Recherches Servier

Beta and Gamma Rhythms Go with the Flow

Information flows through visual areas in opposite directions during “bottom-up” intake of current stimuli and “top-down” processes such as attention or memory. In this issue of Neuron, Bastos et al. (2015) report that rhythms of different frequencies coordinate bottom-up and top-down information streams

Simulating complex conductivity in carbonate rocks: using digital carbonate rocks and comparison to laboratory measurements

Digital rock physics involves the modern microscopic imaging of geomaterials, digitalization of the microstructure, and numerical simulation of physical properties of rocks. This physics-based approach can give important insight into understanding properties of reservoir rocks, and help reveal the link between intrinsic rock properties and macroscopic geophysical responses. Our focus is the simulation of the complex conductivity of carbonate reservoir rocks using reconstructed 3D rock structures from high-resolution X-ray micro computed tomography (micro-CT). Carbonate core samples with varying lithofacies and pore structures from the Cambro-Ordovician Arbuckle Group and the Upper Pennsylvanian Lansing-Kansas City Group in Kansas were used in this study. The wide variations in pore geometry and connectivity of these samples were imaged using micro-CT. A two-phase segmentation method was used to reconstruct a digital rock of solid particles and pores. We then calculated the effective electrical conductivity of the digital rock volume using a pore-scale numerical approach. The complex conductivity of geomaterials is influenced by the electrical properties and geometry of each phase, i.e., the solid and fluid phases. In addition, the electrical double layer that forms between the solid and fluid phases can also affect the effective conductivity of the material. In the numerical modeling, the influence of the electrical double layer is quantified by a complex surface conductance and converted to an apparent volumetric complex conductivity of either solid particles or pore fluid. The effective complex conductivity resulting from numerical simulations were compared to results from laboratory experiments on equivalent rock samples. In general, simulated σ'eff values were below laboratory measurements, while numerical σ''eff values were within reasonable range. The imaging and digital segmentation technique, fundamental rock characteristics, and model assumptions all play an important role in the simulation process

Comparison of human mammary epithelial cells immortalized by simian virus 40 T-Antigen or by the telomerase catalytic subunit

We directly compared two methods of immortalizing human mammary epithelial cells (HMECs). Cells were transfected with an expression plasmid either for hTERT, the catalytic subunit of telomerase, or for the simian virus 40 (SV40) early region genes. Under standard culture conditions, HMECs were not immortalized by hTERT unless they had spontaneously ceased expression of the p16(INK4a) tumor suppressor gene. Untransfected HMECs had low levels of telomerase expression, and immortalization by both methods was associated with an increase in telomerase activity and prevention of telomere shortening. SV40-induced immortalization was accompanied by aberrant differentiation, loss of DNA damage response, karyotypic instability and, in some cases, tumorigenicity. hTERT-immortalized cells had fewer karyotypic changes, but had intact DNA damage responses, and features of normal differentiation. Although SV40-immortalized cells are useful for studies of carcinogenesis, hTERT-immortalized cells retain more properties of normal cells.NHMR

Methodological Caveats in the Detection of Coordinated Replay between Place Cells and Grid Cells

At rest, hippocampal “place cells,” neurons with receptive fields corresponding to specific spatial locations, reactivate in a manner that reflects recently traveled trajectories. These “replay” events have been proposed as a mechanism underlying memory consolidation, or the transfer of a memory representation from the hippocampus to neocortical regions associated with the original sensory experience. Accordingly, it has been hypothesized that hippocampal replay of a particular experience should be accompanied by simultaneous reactivation of corresponding representations in the neocortex and in the entorhinal cortex, the primary interface between the hippocampus and the neocortex. Recent studies have reported that coordinated replay may occur between hippocampal place cells and medial entorhinal cortex grid cells, cells with multiple spatial receptive fields. Assessing replay in grid cells is problematic, however, as the cells exhibit regularly spaced spatial receptive fields in all environments and, therefore, coordinated replay between place cells and grid cells may be detected by chance. In the present report, we adapted analytical approaches utilized in recent studies of grid cell and place cell replay to determine the extent to which coordinated replay is spuriously detected between grid cells and place cells recorded from separate rats. For a subset of the employed analytical methods, coordinated replay was detected spuriously in a significant proportion of cases in which place cell replay events were randomly matched with grid cell firing epochs of equal duration. More rigorous replay evaluation procedures and minimum spike count requirements greatly reduced the amount of spurious findings. These results provide insights into aspects of place cell and grid cell activity during rest that contribute to false detection of coordinated replay. The results further emphasize the need for careful controls and rigorous methods when testing the hypothesis that place cells and grid cells exhibit coordinated replay

Challenges for identifying the neural mechanisms that support spatial navigation: the impact of spatial scale.

Spatial navigation is a fascinating behavior that is essential for our everyday lives. It involves nearly all sensory systems, it requires numerous parallel computations, and it engages multiple memory systems. One of the key problems in this field pertains to the question of reference frames: spatial information such as direction or distance can be coded egocentrically-relative to an observer-or allocentrically-in a reference frame independent of the observer. While many studies have associated striatal and parietal circuits with egocentric coding and entorhinal/hippocampal circuits with allocentric coding, this strict dissociation is not in line with a growing body of experimental data. In this review, we discuss some of the problems that can arise when studying the neural mechanisms that are presumed to support different spatial reference frames. We argue that the scale of space in which a navigation task takes place plays a crucial role in determining the processes that are being recruited. This has important implications, particularly for the inferences that can be made from animal studies in small scale space about the neural mechanisms supporting human spatial navigation in large (environmental) spaces. Furthermore, we argue that many of the commonly used tasks to study spatial navigation and the underlying neuronal mechanisms involve different types of reference frames, which can complicate the interpretation of neurophysiological data