Name of Principal Investigator: Dr Ivan PavlovInstitution: University College LondonYear of award: 2013BackgroundAnti-epileptic drugs successfully control seizures in about two-thirds of people with epilepsy, but because they act on mechanisms that occur throughout the brain, they often cause unwanted side effects (e.g. lethargy, weight gain, personality changes). There is an urgent need for new treatments that target pathways that are specific to epileptic activity, and that do this as early as possible in the lead-up to a seizure. However the ‘events’ that occur just before a seizure are still not fully understood, and this is a major obstacle to progress.The work of Dr Pavlov and colleagues, at University College London, focuses on the activity of inhibitory neurons (which have always been thought to dampen excitability in the brain) before and during a seizure. Recent findings, both by Dr Pavlov’s team and others, suggest that, in certain circumstances, networks of inhibitory neurons may actually promote seizure development. The current project, which aimed to explore this further, is now complete and the final report has been submitted.MethodsDuring the study, the team combined seizure detection methods with a technique called optogenetics, in living and experimental epilepsy models. Optogenetics allows specific groups of neurons to be activated (‘turned on’) or suppressed (‘turned off’), with great accuracy, by flashing light of a certain wavelength on them. This is called ‘photostimulation’. The group used optogenetics to target different types of inhibitory neuron and find out more about their role in seizure activity.FindingsThe group discovered that identical photostimulation could have either a pro-epileptic or anti-epileptic effect, depending on the nature of epileptic activity that was occurring at that time. They also found that suppressing/activating a particular type of inhibitory neuron produced the opposite effect (curbing or promoting epileptic activity) depending on the time since a seizure had begun. In light of these findings, the researchers suggest that, as seizure activity evolves, the contribution of different types of inhibitory neuron changes, and that, therefore, the timing of an intervention, as well as its action, is critical to the effect on epileptic activity.SignificanceThese findings greatly increase our understanding of the events surrounding a seizure, and this will potentially lead to the development of more targeted epilepsy treatments. The hope is that these therapies will be more effective than existing ones, with fewer side effects, and that they will also benefit people whose seizures are currently uncontrolled.