Single Neuron Dynamics in Epilepsy

Epilepsy is one of the most prevalent neurological conditions affecting nearly 65 million people worldwide and is characterized by spontaneous seizures. Seizures in about 70% of the patients can be reduced by anti-epileptic drugs but the remaining patients cannot be helped by current therapies. Lack of effective treatments suggests a need to understand the mechanisms underlying both the acute (status epilepticus) and chronic phase of epilepsy. In some cases, epilepsy can be caused by neurological changes triggered due to an initial event such as brain injury, stroke or fever resulting in continuous seizures i.e. status epilepticus (SE). Within a single episode of SE, seizures become less responsive to drugs due to hitherto unknown reasons. To address this, we recorded population of single neurons and field potentials from hippocampus of rats experiencing SE. Our results show distinct patterns in single neuronal dynamics and field potentials suggesting there may be a loss of inhibition as SE progressed emphasizing the need for monitoring EEGs to provide efficient treatments. In the chronic phase of epilepsy, seizures are isolated and last for a short duration but can happen unexpectedly. Recent studies in animal models demonstrated that theta oscillations precede a majority of seizures and a fraction of interneurons show abnormally high firing at the onset of seizures. To date, in vivo long-term and transient neuronal activity associated with theta oscillations in epileptic animals have not been explained. To address this, we recorded and analyzed populations of single neurons and field potentials during inter-seizure and pre-seizure theta periods in pilocarpine-treated epileptic animals. Results show that in an epileptic network with sustained decrease in excitability, a subset of generally unaffected interneurons with theta-related firing is activated at the onset of seizures. This work offers the first description of sustained and transient changes of in vivo classifiable interneurons during the transition to seizure. By advancing our knowledge of seizure propagation, this information could be used to improve therapeutic intervention strategies.