Institute of Neuroscience

Staff Profile

Professor Andrew Trevelyan

Professor of Network Neuroscience

Research

Recent news (updated Jan 2018)

  • BBSRC grant award (start date, Oct 2017), entitled "Cl-out: a novel cooperative-optogenetic strategy to control neuronal chloride", together with my collaborators Jeremy Lakey and Bob Lightowlers.  We have postdoctoral positions available on this grant, so please get in touch.
  • This grant follows up our recent paper in Nature Communications, describing our now optogenetic tool, Cl-out.  See https://www.nature.com/articles/ncomms13495 (open access)

  • MRC grant award  (start date, Oct 2017), entitled "Changing network interactions in models of medically refractory epilepsy".
  • Wellcome Trust-NIH PhD studentship award: Chris McBain (NIH) and I sponsored Connie Mackenzie-Gray Scott's application for this, and we were delighted that she rose to the challenge at her interview and was awarded this prestigious studentship, to start in Oct 2017.  Well done Connie!.
  • Ryley Parrish won the Basic Sciences Presentation Prize at the UK chapter meeting of the International League Against Epilepsy meeting.  He was describing his work investigating how activity homeostasis in interneurons may be at odds with network homeostasis.  We term this "homeostatic conflict".  This work is funded by a project grant from Epilepsy Research UK.
  • Please have a look at (and then cite!) a review I authored for Trends in Neuroscience article accepted - entitled "Do cortical circuits need protecting from themselves?"  This too is open access, so enjoy.  You can find it at http://www.cell.com/trends/neurosciences/abstract/S0166-2236(16)30053-4
  • I have just made my final visit to Columbia University, as a Schaefer Scholar.  Sorry to see that finish, but ready to refocus on some fantastic projects in Newcastle, including establishing 2-photon microscopy here.   
  • 5 of my doctoral students have recently finished their theses and are stepping out into the world!  
  • Hannah Alfonsa worked on the chloride regulation story (above) and moved on to Oxford.  Last year she was given a prestigious Junior Research Fellowship at St.John's College (my alma mater!), and she followed this up this year, with a Sir Henry Dale Postdoctoral Fellowship (Wellcome Trust).  We're proud of you, Hannah!
  • Ed Merricks defended his thesis in January, and has now moved on to doing a postdoc at one of America's Ivy League, Columbia University, with my long-term collaborator, Cathy Schevon.  
  • Parto Yazdani was awarded her thesis in January.  Her main findings were published earlier this year in Physiological Reports, describing how a simple visual test may shed light into subtle differences in brain function in people with different types of epilepsy.  (http://physreports.physiology.org/content/5/5/e13079.long)  
  • Chris Papasavvas defended in January, 2017, and has just been awarded his thesis.  He has taken up a postdoctoral position, continuing to investigate cortical interneuron function with Leon Lagnado, at Sussex University.
  • And finally, Neela Codadu, who was awarded his PhD earlier this month (Jan, 2018).  He is currently writing up papers and will then join Peter Kind up in Edinburgh, as a postdoc.  Well done all!
  • We also welcome Laura Alberio, who joined us as a postdoc last October, to help develop Cl-out.    She was involved in a fantastic project with Anna Moroni, for her PhD, to develop an optogenetic K channel (Science, 348, 707-10)

Videos of me talking about epilepsy and our research

We filmed a recent public presentation we made at the British Science Festival, and this has now been edited into a film that we have posted on line.  See

https://www.epilepsyresearch.org.uk/tsunamis-in-the-brain/

See also another talk I gave at an International League Against Epilepsy meeting

https://www.epilepsyresearch.org.uk/research/videos/


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.  See

http://www.nature.com/nature/journal/v511/n7508_supp/full/511S4a.html


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.  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 and MRC. 

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.  


(The picture shows the lab members last summer (before Laura joined us), from the left, myself, Claudia Racca, Owain Thomas, Richard Burman (visiitor from Cape Town), Ryley Parrish, Connie Mackenzie-Gray Scott, Rob Graham and Neela Codadu) 

Publications