PhD Study : Correlation between Synchronised Neuronal Burst Firing and Brain Seizures: A Biophysical Model

Summary

Background:

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 [1]. 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 [2]. 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.

Project Aims:

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].

Outcome:

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”.

Resources:

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

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Experience using research methods or other approaches relevant to the subject domain

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Masters at 70%
• For VCRS Awards, Masters at 75%
• Publications - peer-reviewed

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living