Project 2

Mapping variations in seizure susceptibility across the brain to identify seizure highways and hubs

 

Supervisors  

Prof Andrew Trevelyan (andrew.trevelyan@ncl.ac.uk)

Dr Abhi Banerjee (abhi.banerjee@ncl.ac.uk)

Mr Chris Cowie (chris.cowie@ncl.ac.uk)

 

Overview

Background

Most epileptic seizures arise either in the neocortex or the hippocampus.  The site of origin determines many key features of the condition, in each individual patient, including how seizures might be triggered, what premonitory symptoms and signs there are, and also, how it may be treated.  Determining the functional anatomy of the seizures – where the seizures start, and their path through the brain - is of particular importance when the epilepsy does not respond to medical management, because surgical treatments may help.  In the past, this usually entailed resection of the pathological site, but the development of new brain-machine interface technology provides possibilities for entirely new surgical treatments. 

Hypothesis

Different cortical areas may have very different susceptibility to epilepsy, on account of key differences in the local microcircuitry or long-range connectivity across areas. This could create “lines of weakness” through the brain, which represent preferential routes for seizure spread.  If such “seizure highways” exist, these could be important targets for surgical treatment.

Methods

We will test this hypothesis by examining seizure susceptibility simultaneously in different parts of a mouse’s brain, using single-photon widefield microscopy.  When neurons are recruited to a seizure, Ca2+ floods into the cell, and this can be visualised using fluorescent Ca2+ indicators.  We will use Ca2+ imaging in transgenic mice to make video records of how seizures spread through the entire cortex.  We will also use optogenetics, a technique which uses light to control neuronal activity, to assay seizure susceptibility and control the spread of epileptic activity at particular sites, or “choke points”.  In parallel studies, we will use our mouse knowledge to understand specific clinical cases, using recordings from surgically resected human brain tissue. 

The environment

Ours is one of the leading epilepsy research laboratories in the UK, with a long-established reputation of using innovative technologies to shed light onto the basic mechanisms by which seizures start and spread.  

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