Principal Supervisor: Dr Stuart GreenhillLink opens in a new window

Co-supervisor: Dr Petro Lutsyk

PhD project title: The contribution of synaptic plasticity to network oscillations and neuronal development

University of Registration: University of Aston

Project outline:

We are interested in how the brain and its constituent cells use the process of plasticity – the mechanism by which synaptic strengths and weightings are changed in response to activity – to set up, entrain and refine the cortical oscillations which underpin normal neuronal function. By manipulating plasticity and interrupting normal network function at key stages, we will disrupt the establishment of oscillatory activity and interrogate the cellular and molecular responses to this maladaptation. In turn, we will gain better insights into how dysfunction of these oscillations arises due to the ageing process, and how aberrant network activity can eventually contribute to disease states such as epilepsy and schizophrenia.

This project will use novel nanomaterial electrode arrays, alongside a combination of in vivo and in vitro electrophysiology, molecular biology, optogenetics and histology/microscopy to manipulate the plasticity of cortical circuits at critical developmental stages. This can lead to lifelong deficits in plasticity (e.g. Greenhill et al, 2015a) or focus on the alteration of connections in one subtype of cortical neurons (Greenhill et al, 2015b). Using wireless EEG and optogenetic control, we will interfere in normal network function as well as utilising pharmacological compounds to alter plasticity in rats. We will then use a combination of patch-clamp electrophysiology, organotypic culture and our in vitro slice oscillation models (Johnson et al, 2017) to interrogate the cellular, circuit and molecular changes in oscillatory drive arising from these manipulations. We will use novel electrode configurations and nanomaterial approaches to record from slices in culture and during in vitro oscillation experiments, allowing for longitudinal manipulations of cellular and circuit function to be performed in vitro.

The key outcome of this project will be a deeper understanding of the cellular and molecular contributions to oscillatory activity in the somatomotor cortical area, and the hippocampal-entorhinal circuit, and how these can be disrupted or ‘rescued’ by synaptic plasticity manipulation.

References:

Greenhill, S.D. et al (2015a) - Adult cortical plasticity depends on an early postnatal critical period. Science 349(6246), 424-27

Greenhill, S.D. et al (2015b) - Hebbian and homeostatic plasticity mechanisms in regular spiking and intrinsic bursting cells of cortical layer 5. Neuron 88(3), 539-52

Johnson, N.W. et al (2017) - Phase-amplitude coupled persistent theta and gamma oscillations in rat primary motor cortex in vitro. Neuropharmacology 119, 141-156

BBSRC Strategic Research Priority: Understanding the rules of life - Neurosciences and behaviour and Integrated Understanding of health - Ageing

Techniques that will be undertaken during the project:

In vitro and in vivo electrophysiology (EEG, LFP, Patch-clamp, MEA)

Optogenetics and circuit manipulation

Molecular biology and histology

Laser microscopy

Animal behaviour

Novel biocompatible electrode development

Contact: Dr Stuart GreenhillLink opens in a new window