Pathological activity in the brain emerges when neurons coordinate to produce unhealthy population rhythms. To better understand this neuronal coordination and identify “key cells” to target with anti-epileptic therapies, we are working to quantify functional connectivity at the cellular level. We first use voltage-sensitive fluorescent proteins to image epileptiform neuronal activity with extraordinary spatiotemporal resolution.
Next, we compute graphs of excitatory (blue) and inhibitory (red) connectivity during different phases of ictogenesis. Our early work in this area suggests that short-term plasticity drives decreases in inhibitory and increases in excitatory connectivity as seizures approach.
We also quantitatively identify “key cells” using the graph theory statistic betweenness centrality. We hypothesize that these cells, which are consistent from seizure to seizure, serve an elevated role in generating seizures and represent selective targets for anti-epileptic therapies.
