On the mechanisms of cerebellar synaptic plasticity

Changes in the strength of signalling between neurones are thought to provide a cellular substrate for learning and memory. In the cerebellar cortex, raising the frequency and the strength of parallel fibre (PF) stimulation leads to a long-term depression (LTD) of the strength of signalling at the synapse between PFs and Purkinje cells (PCs), which spreads to distant synapses to the same cell via a nitric oxide (NO) dependent mechanism. At the same synapse, but under conditions of reduced post-synaptic calcium activity, raised frequency stimulation (RFS) of PFs triggers a long-term potentiation of synaptic transmission. The aims of the work described in this thesis were to investigate the conditions necessary for LTD and LTP at this synapse following RFS and to identify the origins and second messenger cascades involved in the induction and spread of LTP and LTD. In thin, parasagittal cerebellar slices whole cell patch clamp recordings were made from PCs and the effects of RFS of one of two, independent PF inputs to the same PC were examined under a range of experimental conditions. Under conditions designed to reduce post-synaptic calcium activity, RFS to a single PF input led to LTP and a decreases in paired pulse facilitation (PPF) in both pathways. This heterosynaptic potentiation was prevented by inhibition of protein kinase A (PKA) or by inhibition of NO synthase with either 7-nitroindazole (7-NI) or NG Nitro-L-argenine methyl ester. Inhibition of guanylate cyclase (GC) or protein kinase G (PKG) had no effect. A similar potentiation was observed upon application of the adenylyl cyclase (AC) activator forskolin or the NO donor spermine NONOate. Both of these treatments also resulted in an increase in the frequency of mEPSCs, which provides further evidence for a presynaptic origin of LTP. Forskolin induced potentiation and the increase in mEPSC frequency were blocked by 7-NI. The styryl dye FM1-43, a fluorescent reporter of endo- and exocytosis, was also used to further examine the possible pre-synaptic origins of LTP. RFS or forskolin application enhanced FM1-43 de-staining and NOS inhibitors blocked this effect. Application of NONOate also enhanced FM1-43 de-staining. When post-synaptic calcium activity was less strictly buffered, RFS to a single PF input led to a transient potentiation that was succeeded by LTD in both pathways. This LTD, which resembled previously described forms, was prevented by inhibition of the NO/cGMP/PKG cascade. Modification of the AC/cAMP/PKA cascade had no effect. In summary, the direction of synaptic plasticity at the PF-PC synapse in response to RFS depends largely on the level of post-synaptic calcium activity. LTP and LTD were non-input specific and both forms of plasticity were dependent on NOS activity. Induction of LTP was mediated by a presynaptic mechanism and depended on NO and cAMP production. LTD on the other hand was a post-synaptic process and required activity of the NO/cGMP/PKG signalling cascade.

Experiments and observations on the behaviour and brain of the aging female mouse with special reference to dementia of the Alzheimer type

The objective of this research was to investigate the effects of normal aging and the additional effects of chronic exposure to two experimental diets, one enriched in aluminium, the other enriched in lecithin, on aspects of the behaviour and brain histology of the female mouse. The aluminium diet was administered in an attempt to develop a rodent model of Dementia of the Alzheimer Type (DAT). With normal aging, almost all assessed aspects of behaviour were found to be impaired. As regards cognition, selective impairments of single-trial passive avoidance and Morris place learning were observed. While all aspects of open-field behaviour were impaired, the degree of impairment was directly related to the degree of motoric complexity. Deficits were also observed on non-visual sensorimotor coordination tasks and in olfactory discrimination. Histologically, neuron loss, gliosis, vacuolation and congophilic angiopathy were observed in several of the brain regions/fibre tracts believed to contribute to the control of some of the assessed behaviours. The aluminium treatment had very selective effects on both behaviour and brain histology, inducing several features observed in DAT. Behaviourally, the treatment induced impaired spatial reference memory; reduced ambulation; disturbed olfactory function and induced the premature development of the senile pattern of swimming. Histologically, significant neuron loss and gliosis were observed in the hippocampus, entorhinal cortex, amygdala, medial septum, pyriform and pr-frontal cortex. In addition, the brain distribution of congophilic angiopathy was significantly increased by the treatment. The lecithin treatment had effects on both non-cognitive and cognitive aspects of behaviour. The effects of aging on open-field ambulation and rearing were partially ameliorated by the treatment. A similar effect was observed for single-trial passive avoidance performance. Age-dependent improvements in acquisition/retention were observed in 17-23 month mice and Morris place task performance was improved in 11 and 17 month mice. Histologically, a partial sparing of neurons in the cerebellum, hippocampus, entorhinal cortex and subiculum was observed.

The Library of Birmingham project:lifelong learning for the digital age

The Library of Birmingham (LoB) is a £193million project designed to provide a new space for lifelong learning and knowledge growth, a physical and virtual portal for Birmingham's citizens to the wider world. In cooperation with a range of private, public, and third-sector bodies, as well as individual citizens, the library, due to open in June 2013, will articulate a continuing process of organic growth and emergence. Key delivery themes focus on: arts and creativity, citizenship and community, enterprise and innovation, learning and skills and the new media ecology. A landmark design in the heart of the cultural district of the city, the LoB aims to stimulate sustainable economic growth, urban regeneration and social inclusion by offering a wide range of new digital learning services, real and virtual community spaces, and new opportunities for interpreting and exploiting internationally significant collections of documentary archives, photography, moving image, and rare printed books. Additionally, the LoB will offer physical space for creative, cultural, enterprise, and knowledge development. This paper outlines the cultural and educational thinking that informs the project and the challenges experienced in developing innovative service redesign.

Experiential learning:inspiring the business leaders of tomorrow

Purpose: The complex challenges of sustainable development and the need to embed these issues effectively into the education of future business leaders has never been more urgent. The purpose of this paper is to discuss different approaches taken by two UK signatories to the UN Principles for Responsible Management Education (PRME). Design/methodology/approach: The two approaches examined are: MSc Entrepreneurship students opting for placements with social enterprises; and MBA students undertaking workshops using "live" case studies. A content analysis of the experiences of students from their written reflective narratives is presented. This is supplemented by reflections of the facilitators and tutors. Findings: The analysis reveals that the opportunity to work with social entrepreneurs and/or "responsible" business professionals provides the business students with inspirational role models and positive social learning opportunities. Research limitations/implications: This paper suggests that experiential learning is an effective way of integrating ethics, responsibility and sustainability into the curriculum but the research draws on the experience of two schools. Further research is important to explore these findings in other contexts. Practical implications: The authors argue that direct exposure to a business culture (and/or behaviour) that is predicated upon ethical/social responsibility and sustainability is an effective means to embed these values in the curriculum. Originality/value: This paper contributes by drawing on social psychological research related to behaviour change to examine how experiential learning on traditional Business Masters programmes can provide students with the knowledge, motivation and skills to contribute positively to society, in a way that more traditional pedagogies cannot. © Emerald Group Publishing Limited.

Was it good for them? Reflections on the use of MENTOR and changes in course design using general performance measures

This paper considers the use of general performance measures in evaluating specific planning and design decisions in higher education and reflects on the students' learning process. Specifically, it concerns the use of the MENTOR multimedia computer aided learning package for helping students learn about OR as part of a general business degree. It includes the transfer of responsibility for a learning module to a new staff member and a change from a single tutor to a system involving multiple tutors. Student satisfaction measures, learning outcome measures and MENTOR usage patterns are examined in monitoring the effects of the changes in course delivery. The results raise some questions about the effectiveness of general performance measures in supporting specific decisions relating to course design and planning.

A pre-post test evaluation of the impact of the PELICAN MDT-TME development programme on the working lives of colorectal cancer team members

Background - The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT-TME) Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer team members. Methods - The impact of participating in the programme on team members' self-reported job stress, job satisfaction and team performance was assessed in a pre-post course study. 333/568 (59%) team members, from the 75 multidisciplinary teams who attended the final year of the Programme, completed questionnaires pre-course, and 6-8 weeks post-course. Results - Across all team members, the main sources of job satisfaction related to working in multidisciplinary teams; whilst feeling overloaded was the main source of job stress. Surgeons and clinical nurse specialists reported higher levels of job satisfaction than team members who do not provide direct patient care, whilst MDT coordinators reported the lowest levels of job satisfaction and job stress. Both job stress and satisfaction decreased after participating in the Programme for all team members. There was a small improvement in team performance. Conclusions - Participation in the Development Programme had a mixed impact on the working lives of team members in the immediate aftermath of attending. The decrease in team members' job stress may reflect the improved knowledge and skills conferred by the Programme. The decrease in job satisfaction may be the consequence of being unable to apply these skills immediately in clinical practice because of a lack of required infrastructure and/or equipment. In addition, whilst the Programme raised awareness of the challenges of teamworking, a greater focus on tackling these issues may have improved working lives further.

“Showing off” your mobile device:adult literacy learning in the classroom and beyond

For a very large number of adults, tasks such as reading. understanding, and using everyday items are a challenge. Although many community-based organizations offer resources and support for adults with limited literacy skills. current programs have difficulty reaching and retaining those that would benefit most. In this paper we present the findings of an exploratory study aimed at investigating how a technological solution that addresses these challenges is received and adopted by adult learners. For this, we have developed a mobile application to support literacy programs and to assist low-literacy adults in today's information-centric society. ALEX© (Adult Literacy support application for Experiential learning) is a mobile language assistant that is designed to be used both in the classroom and in daily life in order to help low-literacy adults become increasingly literate and independent. Through a long-term study with adult learners we show that such a solution complements literacy programs by increasing users' motivation and interest in learning, and raising their confidence levels both in their education pursuits and in facing the challenges of their daily lives.

On the Quality of Decision Functions in Pattern Recognition

The problem of decision functions quality in pattern recognition is considered. An overview of the approaches to the solution of this problem is given. Within the Bayesian framework, we suggest an approach based on the Bayesian interval estimates of quality on a finite set of events.

Sizing energy storage on the 11kV distribution network

The cost and limited flexibility of traditional approaches to 11kV network reinforcement threatens to constrain the uptake of low carbon technologies. Ofgem has released £500m of funding for DNOs to trial innovative techniques and share the learning with the rest of the industry. One of the techniques under study is the addition of Energy Storage at key substations to the network to help with peak load lopping. This paper looks in detail at the sizing algorithm for use in the assessment of alternatives to traditional reinforcement and investigates a method of sizing a battery for use on a Network taking into account load growth, capacity fade and battery lifecycle issues. A further complication to the analysis is the method of operation of the battery system and how this affects the Depth of Discharge (DoD). The proposed method is being trialled on an area of 11kV network in Milton Keynes Central area and the simulation results are presented in this paper.

Exploration by Means of Computer Simulation of Nonlinear Hierarchical Structure of Neuronal Memory on the Model of Olfactory Bulb

Results of numerical experiments are introduced. Experiments were carried out by means of computer simulation on olfactory bulb for the purpose of checking of thinking mechanisms conceptual model, introduced in [2]. Key role of quasisymbol neurons in processes of pattern identification, existence of mental view, functions of cyclic connections between symbol and quasisymbol neurons as short-term memory, important role of synaptic plasticity in learning processes are confirmed numerically. Correctness of fundamental ideas put in base of conceptual model is confirmed on olfactory bulb at quantitative level.

e-Learning, e-Practising and e-Tutoring: an Integrated Approach

In this paper is described a didactic methodology combining current e-learning methods and the support of Intelligent Agents technologies. The aim is to favor the synthesis among theoretical approach and based practical approach using the so-called Intelligent Agent, software that exploits the Artificial Intelligence and that operates as tutor, facilitating the consumers in the training operations. The paper illustrates how such new Intelligent Agent algorithm (IA) is used in the training of employees working in the transportation sector, thanks to the experience gained with the PARMENIDE project - Promoting Advanced Resources and Methodologies for New Teaching and Learning Solutions in Digital Education.

A sphere of resonance for networked learning in the ‘non-places’ of our universities

The logic of ‘time’ in modern capitalist society appears to be a fixed concept. Time dictates human activity with a regularity, which as long ago as 1944, George Woodcock referred to as The Tyranny of the Clock. Seventy years on, Hartmut Rosa suggests humans no longer maintain speed to achieve something new, but simply to preserve the status quo, in a ‘social acceleration’ that is lethal to democracy. Political engagement takes time we no longer have, as we rush between our virtual spaces and ‘non-places’ of higher education. I suggest it’s time to confront the conspirators that, in partnership with the clock, accelerate our social engagements with technology in the context of learning. Through Critical Discourse Analysis (CDA) I reveal an alarming situation if we don’t. With reference to Bauman’s Liquid Modernity, I observe a ‘lightness’ in policy texts where humans have been ‘liquified’ Separating people from their own labour with technology in policy maintains the flow of speed a neoliberal economy demands. I suggest a new ‘solidity’ of human presence is required as we write about networked learning. ‘Writing ourselves back in’ requires a commitment to ‘be there’ in policy and provide arguments that decelerate the tyranny of time. I am though ever-mindful that social acceleration is also of our own making, and there is every possibility that we actually enjoy it.

Manifold learning and the quantum Jensen-Shannon divergence kernel

The quantum Jensen-Shannon divergence kernel [1] was recently introduced in the context of unattributed graphs where it was shown to outperform several commonly used alternatives. In this paper, we study the separability properties of this kernel and we propose a way to compute a low-dimensional kernel embedding where the separation of the different classes is enhanced. The idea stems from the observation that the multidimensional scaling embeddings on this kernel show a strong horseshoe shape distribution, a pattern which is known to arise when long range distances are not estimated accurately. Here we propose to use Isomap to embed the graphs using only local distance information onto a new vectorial space with a higher class separability. The experimental evaluation shows the effectiveness of the proposed approach. © 2013 Springer-Verlag.

Comparing Several Methods of Discriminant Analysis on the Case of Wine Data

2000 Mathematics Subject Classification: 62H30, 62J20, 62P12, 68T99