How do seizures start in the brain? This question remains one of the greatest mysteries in neurology, and without an answer we are limited in our ability to develop more effective epilepsy treatments. Although the past decade has brought tremendous advances in diagnostic and therapeutic tools for epilepsy, we still do not know which specific circuit elements to target.
Investigation of neuronal circuits in epilepsy has been limited by significant technical challenges: First, different neuron types are intermingled in the brain, such that it is difficult to selectively isolate an individual cell type experimentally. Second, epilepsy is a dynamic condition, with seizures emerging suddenly from baseline brain activity, such that static measurements may not be adequate to understand seizures.
We now have the tools to overcome these challenges. Pre-clinical mouse models of epilepsy can be coupled with Cre-driver lines, allowing genetic access to specific cell types. Within these defined cell types, we can selectively express molecular tools that allow us to dynamically measure (e.g., via 2-photon calcium imaging) or manipulate (e.g., via optogenetics or chemogenetics) neuronal firing during seizures.