Information transmission in the nervous system relies on synaptic connections between neurons. While the strength of these connections is constantly changing through activity-dependent plasticity, the output of large neuronal networks is reliable over time. Homeostatic plasticity ensures network activity remains within physiological boundaries by modulating cellular excitability and strength of synaptic connections. In some cases, homeostatic mechanisms fail to regulate the level of neuronal activity leading to epileptiform discharges.
This project will use electrophysiology, optical imaging and electron microscopy to assess functional and structural changes occurring at presynaptic terminals and their effect on network excitability. Previous work in the lab has shown changes in vesicular organization in a mouse model of focal epilepsy. The project will build on these results to study fundamental aspects of synaptic function and their role in regulating network activity in healthy and epileptic brains.
The student will receive training in a wide range of techniques including: electrophysiology (patch clamp and extracellular recordings), live fluorescence imaging (calcium and vesicular imaging), functional labelling for electron microscopy and the use of computational tools for the analysis of large datasets.
For more information please contact directly the supervisor: Vincenzo Marra vm120@leicester.ac.uk
Start date: October 2018
The studentship includes fees, stipend and training funds for 4 years.
References:
Marra V., Burden J.J., Thorpe J.R., Smith I., Smith S.L., Häusser M., Branco T., Staras K. A preferentially segregated recycling vesicle pool of limited size supports neurotransmission in native central synapses. Neuron. 2012 Nov 8;76(3):579-89.
Ratnayaka A.*, Marra V.*, Branco T., Staras K. Extrasynaptic vesicle recycling in mature hippocampal neurons. Nat Commun. 2011 Nov 8;2:531.
Marra, V., Burden, J. J., Crawford, F. & Staras, K. Ultrastructural readout of functional synaptic vesicle pools in hippocampal slices based on FM dye labelling and photoconversion. Nat Protoc 2014 9, 1337-1347.
Steinert J.R., Robinson S.W., Tong H., Haustein M.D., Kopp-Scheinpflug C., Forsythe I.D. Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability. Neuron. 2011 July 28;71(2-3):291-305.
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