Professor Andrew Trevelyan
Professor of Network Neuroscience
- Email: email@example.com
- Telephone: +44 (0) 191 208 5732
- Fax: +44 (0) 191 208 5227
- Address: Room MG162
Institute of Neuroscience,
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
See also another talk I gave at an International League Against Epilepsy meeting
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
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)
- Parrish RR, Grady J, Codadu NK, Trevelyan AJ, Racca C. Simultaneous profiling of activity patterns in multiple neuronal subclasses. Journal of Neuroscience Methods 2018, epub ahead of print.
- Yazdani P, Read JCA, Whittaker RG, Trevelyan AJ. Assessment of epilepsy using noninvasive visual psychophysics tests of surround suppression. Physiological Reports 2017, 5(5), e13079.
- Wang Y, Trevelyan AJ, Valentin A, Alarcon G, Taylor PN, Kaiser M. Mechanisms underlying different onset patterns of focal seizures. PLoS Computational Biology 2017, 13(5), e1005475.
- Alfonsa H, Lakey JH, Lightowlers RN, Trevelyan AJ. Cl-out is a novel cooperative optogenetic tool for extruding chloride from neurons. Nature Communications 2016, 7, 13495.
- Trevelyan AJ. Do Cortical Circuits Need Protecting from Themselves?. Trends in Neuroscience 2016, 39(8), 502-511.
- Smith EH, Liou JY, Davis TS, Merricks EM, Kellis SS, Weiss SA, Greger B, House PA, McKhann GM, Goodman RR, Emerson RG, Bateman LM, Trevelyan AJ, Schevon CA. The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures. Nature Communications 2016, 7, 11098.
- Papasavvas CA, Wang Y, Trevelyan AJ, Kaiser M. Gain control through divisive inhibition prevents abrupt transition to chaos in a neural mass model. Physical Review E 2015, 92(3), 032723.
- Read JCA, Georgiou R, Brash C, Yazdani P, Whittaker R, Trevelyan A, Serrano-Pedraza I. Moderate acute alcohol intoxication has minimal effect on surround suppression measured with a motion direction discrimination task. Journal of Vision 2015, 15(1), 5.
- Stoll EA, Makin R, Sweet IR, Trevelyan AJ, Miwa S, Horner PJ, Turnbull DM. Neural stem cells in the adult subventricular zone oxidize fatty acids to produce energy and support neurogenic activity. Stem Cells 2015, 33(7), 2306-2319.
- Weiss SA, Lemesiou A, Connors R, Banks GP, McKhann GM, Goodman RR, Zhao BS, Filippi CG, Nowell M, Rodionov R, Diehl B, McEvoy AW, Walker MC, Trevelyan AJ, Bateman LM, Emerson RG, Schevon CA. Seizure localization using ictal phase-locked high gamma: A retrospective surgical outcome study. Neurology 2015, 84(23), 2320-2328.
- Merricks EM, Smith EH, McKhann GM, Goodman RR, Bateman LM, Emerson RG, Schevon CA, Trevelyan AJ. Single unit action potentials in humans and the effect of seizure activity. Brain 2015, 138(10), 2891-2906.
- Alfonsa H, Merricks EM, Codadu NK, Cunningham MO, Deisseroth K, Racca C, Trevelyan AJ. The Contribution of Raised Intraneuronal Chloride to Epileptic Network Activity. Journal of Neuroscience 2015, 35(20), 7715-7726.
- Trevelyan A, Muldoon SF, Merricks EM, Racca C, Staley K. The Role of Inhibition in Epileptic Networks. Journal of Clinical Neurophysiology 2015, 32(3), 227-234.
- Yazdani P, Serrano-Pedraza I, Whittaker RG, Trevelyan A, Read JC. Two common psychophysical measures of surround suppression reflect independent neuronal mechanisms. Journal of Vision 2015, 15(13).
- Trevelyan AJ, Schevon CA. How inhibition influences seizure propagation. Neuropharmacology 2013, 69, 45-54.
- Weiss SA, Banks GP, McKhann GM, Goodman RR, Emerson RG, Trevelyan AJ, Schevon CA. Ictal high frequency oscillations distinguish two types of seizure territories in humans. Brain 2013, 136(12), 3796-3808.
- Trevelyan AJ, Bruns W, Mann EO, Crepel V, Scanziani M. The information content of physiological and epileptic brain activity. The Journal of Physiology 2013, 591(4), 799-805.
- Schevon CA, Weiss S, McKhann G, Goodman RR, Yuste R, Emerson RG, Trevelyan AJ. Evidence of an inhibitory restraint of seizure activity in humans. Nature Communications 2012, 3, 1060.
- Ali H, Forraz N, McGuckin C, Jurga M, Lindsay S, Ip BK, Trevelyan A, Basford C, Habibollah S, Ahmad S, Clowry GJ, Bayatti N. In vitro modelling of cortical neurogenesis by sequential induction of human umbilical cord blood stem cells. Stem Cell Reviews and Reports 2012, 8(1), 210-223.
- Jurga M, Forraz N, Basford C, Atzeni G, Trevelyan AJ, Habibollah S, Ali H, Zwolinski SA, McGuckin CP. Neurogenic Properties and a Clinical Relevance of Multipotent Stem Cells Derived from Cord Blood Samples Stored in the Biobanks. Stem Cells and Development 2012, 21(6), 923-936.
- Prida L, Trevelyan AJ. Cellular mechanisms of high frequency oscillations in epilepsy: on the diverse sources of pathological activities. Epilepsy Research 2011, 97(3), 308-317.
- Trevelyan AJ, Kirby DM, Smulders-Srinivasan TK, Nooteboom M, Acin-Perez R, Enriquez JA, Whittington MA, Lightowlers RN, Turnbull DM. Mitochondrial DNA mutations affect calcium handling in differentiated neurons. Brain 2010, 133(3), 787-796.
- Trevelyan A, Yuste R. Imaging seizure propagation in vitro. Neuromethods 2009, 40, 141-161.
- Schevon CA, Trevelyan AJ, Schroeder CE, Goodman RR, McKhann G, Emerson RG. Spatial characterization of interictal high frequency oscillations in epileptic neocortex. Brain 2009, 132(11), 3047-3059.
- Trevelyan AJ. The Direct Relationship between Inhibitory Currents and Local Field Potentials. Journal of Neuroscience 2009, 29(48), 15299-15307.
- Trevelyan AJ, Upton AL, Cordery PM, Thompson ID. An experimentally induced duplication of retinotopic mapping within the hamster primary visual cortex. European Journal of Neuroscience 2007, 26(11), 3277-3290.
- Trevelyan AJ, Sussillo D, Yuste R. Feedforward inhibition contributes to the control of epileptiform propagation speed. Journal of Neuroscience 2007, 27(13), 3383-3387.
- Trevelyan AJ, Baldeweg T, Van Drongelen W, Yuste R, Whittington M. The source of afterdischarge activity in neocortical tonic-clonic epilepsy. Journal of Neuroscience 2007, 27(49), 13513-13519.
- Trevelyan AJ, Sussillo D, Watson BO, Yuste R. Modular propagation of epileptiform activity: Evidence for an inhibitory veto in neocortex. Journal of Neuroscience 2006, 26(48), 12447-12455.