Synaptic Neurology

A specific class of brain cells called neurogliaform cells may play a key role in how epileptic seizures start and spread. The research team will test this by genetically targeting these cells in mice and recording their activity during seizures. This matters because current epilepsy treatments often fail—roughly one in three patients does not respond to medication. The problem is that scientists do not fully understand how normal brain activity tips into the pathological, synchronised firing that characterises a seizure. The team will also investigate two other mechanisms thought to perpetuate seizures: chloride shifts that make inhibitory signals excitatory, and a phenomenon called depolarisation block where interneurons stop firing altogether. By combining optogenetics—using light to switch neurons on or off—with simultaneous imaging of the neurotransmitters GABA and glutamate, they can watch these processes unfold in real time in awake animals. If successful, this work could reveal new targets for seizure-stopping interventions, such as boosting the chloride transporter KCC2 to restore normal inhibition. The research is primarily fundamental science, aimed at understanding the circuit-level logic of seizure perpetuation. But deeper knowledge of how specific interneuron subtypes fail during seizures could eventually lead to more precise therapies for the hundreds of thousands of people with drug-resistant epilepsy.