Investigations into the cellular and molecular changes in the amygdala in models of temporal lobe epilepsy and maternal immune activation

The amygdala is a limbic structure that is involved in many of our emotions and processing of these emotions such as fear, anger and pleasure. Conditions such as anxiety, autism, and also epilepsy, have been linked to abnormal functioning of the amygdala, owing to improper neurodevelopment or damage. This thesis investigated the cellular and molecular changes in the amygdala in models of temporal lobe epilepsy (TLE) and maternal immune activation (MIA). The kainic acid (KA) model of temporal lobe epilepsy (TLE) was used to induce Ammon’s-horn sclerosis (AHS) and to investigate behavioural and cytoarchitectural changes that occur in the amygdala related to Neuropeptide Y1 receptor expression. Results showed that KA-injected animals showed increased anxiety-like behaviours and displayed histopathological hallmarks of AHS including CA1 ablation, granule cell dispersion, volume reduction and astrogliosis. Amygdalar volume and neuronal loss was observed in the ipsilateral nuclei which was accompanied by astrogliosis. In addition, a decrease in Y1 receptor expressing cells in the ipsilateral CA1 and CA3 sectors of the hippocampus, ipsi- and contralateral granule cell layer of the dentate gyrus and ipsilateral central nucleus of the amygdala was found, consistent with a reduction in Y1 receptor protein levels. The results suggest that plastic changes in hippocampal and/or amygdalar Y1 receptor expression may negatively impact anxiety levels. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and tight regulation and appropriate control of GABA is vital for neurochemical homeostasis. GABA transporter-1 (GAT-1) is abundantly expressed by neurones and astrocytes and plays a key role in GABA reuptake and regulation. Imbalance in GABA homeostasis has been implicated in epilepsy with GAT-1 being an attractive pharmacological target. Electron microscopy was used to examine the distribution, expression and morphology of GAT-1 expressing structures in the amygdala of the TLE model. Results suggest that GAT-1 was preferentially expressed on putative axon terminals over astrocytic processes in this TLE model. Myelin integrity was examined and results suggested that in the TLE model myelinated fibres were damaged in comparison to controls. Synaptic morphology was studied and results suggested that asymmetric (excitatory) synapses occurred more frequently than symmetric (inhibitory) synapses in the TLE model in comparison to controls. This study illustrated that the amygdala undergoes ultrastructural alterations in this TLE model. Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders such as autism, schizophrenia and also epilepsy. MIA was induced at a critical window of amygdalar development at E12 using bacterial mimetic lipopolysaccharide (LPS). Results showed that MIA activates cytokine, toll-like receptor and chemokine expression in the fetal brain that is prolonged in the postnatal amygdala. Inflammation elicited by MIA may prime the fetal brain for alterations seen in the glial environment and this in turn have deleterious effects on neuronal populations as seen in the amygdala at P14. These findings may suggest that MIA induced during amygdalar development may predispose offspring to amygdalar related disorders such as heightened anxiety, fear impairment and also neurodevelopmental disorders.

IS capability assessment - the MIND canvas

With the increasing ubiquity and growing pervasiveness of Information Systems (IS) in todays’ organisations, one of the capabilities of essential value to an organisation is its IS/IT (henceforth IS) capability. However, despite this increasing importance of the IS capability, research has barely focused on providing a measure for assessing the IT capability of an organization. In overview, IS capability has contributed significantly in understanding how information technology remains a valuable component of any modern day firm (Bharadwaj 2000, Santhanam and Hartono 2003). While these prior research focus in itself is of value in establishing the importance of IS capability, this current study posits that this research area is attaining maturity and it is about time we extend this stream to provide a measure for assessing and evaluating the IS capability that defines an organization. To borrow a quote from Peter Drucker - “if it can be measured; it can be improved”.

Zazen, philosophy of mind, and the practicality of realising impermanence

This dissertation involves a general overview of the meditative practice of zazen and analytic philosophy of mind while suggesting a potential bridge between them in the form of an analysis of the practicality of realising impermanence. By the end of my argument I hope to have offered up some compelling evidence in favour of the idea that analytic philosophy would benefit greatly from adopting principles which are best learned and expressed through the practice of, and scholarship around, Zen Buddhism and in particular the treatment of the concept of impermanence. I demonstrate the Western philosophical tendency to make dichotomous assumptions about the nature of mind, even when explicitly denying a dualist framework. I do so by examining the historical and philosophical precedent for dualistic thinking in the work of figures such as Plato and Descartes. I expand on this idea by examining the psychology of categorisation - i.e. creating mental categories and boundaries - and demonstrating how such categorisations feeds back into behaviour in practical ways, both positive and negative. The Zen Buddhist principle of impermanence states that all phenomena are impermanent and therefore lack essential nature; this includes intellectual concepts such as the metaphysical framework of the analytic approach to mind. Impermanence is a principle which is realised through the embodied practice of zazen. By demonstrating its application to analytic philosophy of mind I show that zazen (and mindfulness practice in general) provides an ongoing opportunity for clearing up entrenched world views, metaphysical assumptions and dogmatic thinking. This in turn may promote a more holistic and ultimately more rewarding comprehension of the role of first-person experience in understanding the world. My argument is not limited to analytic philosophy of mind but reflects broad aspects of thinking in general, and I explain its application to issues of social importance, in particular education systems.