Seizures are the hallmark of epilepsy, and are generated by hyper-synchronous discharges of populations of neurons. It is known that GABA release from GABA interneurons synchronises principal cell population discharge, contributing to the generation of rhythmic activity in neuronal networks, such as theta and gamma frequency oscillations . It is also believed that this rhythmic activity may be linked to GABA released in proximity to an astrocyte: this signalling pathway is known to regulate synaptic transmission . To advance our understanding of seizure activity requires a biophysical model that captures interactions between a GABA interneuron, an astrocyte terminal and the pre and postsynaptic neuronal terminals. This sets the focus for the following project.
The principle aim of this project is to (i) develop a novel biophysical model that describes the signalling pathways at the tripartite synapse and (ii) use the model to advance our understanding of the biophysical mechanisms underpinning synchronised neuronal burst firing. This work builds on recent research involving the CNET research group based at Ulster University, Department of Neuroscience at the University of Minnesota, USA and the Royal College of Surgeons (RCSI), Dublin [3,4].
This project will develop a cellular level model to test the hypothesis that GABA released from GABA interneurons regulates synchronised neuronal burst firing. The potential outcome of this research will provide a transformative understanding with regards the generation of normal and pathologic neural circuit behaviour, relevant to brain diseases that feature altered synaptic properties or where there is a propensity for the episodic synchronised bursting behaviour of neurons. The relevance of GABA-B signalling via astrocytes to the generation of certain frequencies in the EEG will also be explored using the model. Furthermore a real outcome is to offer therapeutic insights through targeted manipulation of the astrocytic GABA-B followed by evaluation of the resting EEG, and investigating whether this alters the frequency or occurrence of pathophysiological neuronal firing and seizures.
The PhD student will:
1.carry out a detailed review of the subject domain: to include the current understanding of GABA signalling at the tripartite synapse.
2.develop a biophysical model of GABA regulation of synaptic plasticity at cellular and network level.
3.use the model to address a fundament question, “what are the biophysical mechanisms underpinning synchronised neuronal burst firing”.
The PhD student will be supported by staff/RA’s/PhD students within CNET, University of Minnesota and RCSI. Also available to the candidate are MATLAB/C/C++/Python and cluster computing
If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.
Vice Chancellors Research Scholarships (VCRS)
The scholarships will cover tuition fees and a maintenance award of £14,777 per annum for three years (subject to satisfactory academic performance). Applications are invited from UK, European Union and overseas students.
The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 14,777 per annum for three years. EU applicants will only be eligible for the fees component of the studentship (no maintenance award is provided). For Non EU nationals the candidate must be "settled" in the UK.
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