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Staff Profile

Professor Andrew Trevelyan

Professor of Network Neuroscience

  • Telephone: +44 (0) 191 208 5732
  • Address: Room MG162
    Medical School
    Framington Place
    NE2 4HH
Background

My primary research interest concerns how the brain regulates its activity levels.  Specifically, I have focused upon the neocortex and hippocampus, which are the parts of the brain concerned with higher cognitive function.  These are also the parts of the brain that are susceptible to epileptic activity, and a major part of my research involves trying to understand how and why epileptic seizures occur.  I am a clinically trained researcher, and worked briefly as a junior neurologist and neurosurgeon, although I no longer practice clinical medicine, choosing instead to do full-time neuroscientific research.

I am a current member of the Scientific Advisory Committee for Epilepsy Research UK.  I have held personal fellowships for my epilepsy work on both sides of the Atlantic, and was awarded a Schaefer Scholarship at Columbia University in 2016. I have published many papers on epileptic pathophysiology in Nature Communications, Brain, Journal of Neuroscience and Journal of Physiology among others.  I have also transcribed an electrophysiological recording of a seizure into a short piece of classical music.  A recording of this can be heard here (from ~9mins into video) together with a description of how it was achieved.  

Particular research highlights include the following:

  • I was the first to use using network Ca2 imaging to visualise a propagating ictal wave, leading to clinically important insights for surgical seizure localization.
  • This work introduced the concepts of the “ictal core” and “ictal penumbra” (terminology that I coined) for the characterization of the spatial and temporal dynamics of seizure propagation.
  • I have developed novel approaches for manipulating chloride levels in neurons, using optogenetics, in order to understand how chloride levels influence synaptic inhibitory function in physiology and disease.
  • Latterly, we have addressed the role of dendritic excitability in creating a tipping point that defines the onset of a seizure.

We use many different experimental techniques in our research, including cellular and network electrophysiological recordings, optogenetics, microscopy, and computational simulations.

PhDs in Epilepsy at Newcastle University

We were recently awarded funds from ERUK (with matched funds from Newcastle University) to set up a Doctoral Training Programme in Epilepsy Research. More details can be found here.


Google Scholar: Click here.

Research

Recent news (updated Jan 2022)

  • The big news, just now is that we are advertising up to 6 PhD studentships for epilepsy research here at Newcastle University.  These will be funded by Epilepsy Research UK (with matched funds from the University), starting in autumn, 2022.  Click here for more details.

  • Connie Mackenzie-Gray-Scott and Ryley Parrish have had a paper accepted in J.Neurophys.  In it, they describe the surprising finding that knocking down PGC1a (a gene involved in matching energy supplies to activity levels in cells) in an important subclass of cortical interneuron, reduces the susceptibilty to epileptic activation.  You can read the full paper here.

  • Rob Graham defended his PhD last year (examined by Mike Hausser and Andy Jackson). The main finding was that optogenetic stimulation of cortical networks reveals a cryptic "tipping point" that heralds the imminent start of seizure activity in a wide range of experimental models of induced seizures.  The tipping point reflects a shift in dendritic excitability, with the stimulation starting to trigger dendritic plateau potentials.  We show how this shift relates to other factors that have been implicated in seizure initiation, to provide a coherent explanation of this critical moment in the pathophysiological process.  You can read a preprint of this work here - it has been submitted for full peer review.
  • Rob has now taken up a postdoctoral position at UCL, with Vincent Magloire and Dimitri Kullmann.  Good luck with that!

  • Laura Alberio was awarded a Newcastle University Faculty Fellowship, which has recently been extended.  Since joining the lab, she has helped established 2-photon imaging, and is progressing well with some exciting studies regarding Cl regulation in cortical neurons. 

  • Darren Walsh and Elaine McDermott have both recently left the lab.  Darren has taken up a postdoc position in Edinburgh with Peter Kind, while Elaine is pursuing her hobbies, in retirement.  It was great having you in the lab.

  • Mukilan Suresh has started his PhD studies in the lab, winning one of the BBSRC-DTP PhD studentships.  He will be co-supervised by my old colleague, Prof Jenny Read, and Drs Vivek Nityananda and Olena Riabinina (Durham), and will be trying to dissect out the stereopsis mechanism in praying mantids, using Ca2 imaging.  This is a big change in research direction for me, but builds upon remarkable work that Jenny, Vivek and their team have done in recent years.  All very exciting and we are thrilled to have Mukilan join us.

  • Welcome to Amy Marshall, who has joined the other lab members (Drs Laura Alberio, Faye McLeod, and Connie Mackenzie-Gray-Scott) for the next year, to help with the Cl-out project.


Videos of me talking about epilepsy and our research

We filmed a public presentation we made at the 2013 British Science Festival, and this has now been edited into a film that we have posted on-line (click here)

 

Feature about my work in Nature

Our studies about the nature of epileptic spread were the main focus of a recent review article in Nature.  (click here)

 

Some more information about my research

When the brain is working normally, very small numbers of brain cells are active at any given time.  Furthermore, the activity is kept tightly focussed as it flows through successive brain regions and is not allowed to spread out, in much the same way as water flowing in a river. 

The banks of the river determine where water can flow.  In the brain, the same job is done by a group of brain cells called inhibitory interneurons.  These brain cells allow activity to spread in one direction, but not to spread out sideways.  However, like a flood occurring when a bank is breached, these interneurons can fail too with similarly disastrous consequences.  Activity spreads out sideways, too many cells become active at once and an epileptic seizure is the result. 

A question I am trying to address in my research is what makes a brain seize.  Starting with tissue from a normal brain, one can increase the likelihood of “seizures” occurring, by changing the solution which bathes the neurons. After changing the solution, there is a very interesting transition period when the tissue behaves as if it were experiencing surges of activity, which are then overcome.  It is as if there are crises in the tissue, which are brought under control by the action of some powerful inhibition restraints.  I believe these restraints are rather like circuit breakers in electrical appliances, and my research has been directed at identifying which cells in the brain fulfil this role.

I am also interested in how these cells regulate activity in the brain.  This question is a fundamental one, addressing why cerebral cortex is built the way it is (see my review article in Trends in Neuroscience).  Furthermore, I want to understand the different ways in which these regulatory functions may break down.  We are also learning how to recognize when this pathology develops in humans.  For instance, we are using our insights from basic animal studies to learn how to interpret EEG recordings (electroencephalograms), one of the cornerstones of epilepsy diagnosis. 

A major effort in our lab is now invested in developing optogenetic strategies to investigate cortical function, and in particular to understand epilepsy and learn how we might manage it.  Last year, we developed a brand new optogenetic tool, designed to drive chloride out of neurons.  The build-up of chloride in neurons is thought to be involved in many epileptic conditions, and whilst there are drugs that try to limit this build up, once the chloride is inside the neurons there had been no way to extrude it.  This was the motivation for developing an optogenetic solution, which we called "Cl-out" (Alfonsa et al, (2016) Nature Communications).  We are continuing to develop this technology, funded through the grants from BBSRC. 

Part of this work is funded by a large grant, CANDO ("Controlling Abnormal Network Dynamics with Optogenetics", see http://www.cando.ac.uk/) involving 12 other Principal Investigators including clinical and non-clinical epilepsy researchers, bio-engineers manufacturing new LED / recording devices for implants into humans, experts in brain-machine interfaces, computational experts and molecular biologists developing new gene therapies.  

Particular research highlights include the following (links are provided to open access publications - please contact me for pdfs for any that you cannot access):

  1. I was the first to use using network Ca2 imaging to visualise a propagating ictal wave, leading to clinically important insights for surgical seizure localization.

The key papers are

Trevelyan et al., 2006

Trevelyan et al. 2007

Schevon et al., 2012

 

  1. This work introduced the concepts of the “ictal core” and “ictal penumbra” (terminology that I coined) for the characterization of the spatial and temporal dynamics of seizure propagation.

See

Schevon et al., 2012

Trevelyan & Schevon, 2013 (review)

Weiss et al, 2014

 

  1. I have developed novel approaches for manipulating chloride levels in neurons, using optogenetics, in order to understand how chloride levels influence synaptic inhibitory function in physiology and disease.

See

Alfonsa et al., 2015 and 2016

 

  1. Latterly, we have addressed the role of dendritic excitability in creating a tipping point that defines the onset of a seizure.

See Graham et al., - preprint posted here; currently under peer review



Publications