A portion of inhibitory neurons in human temporal lobe epilepsy are functionally upregulated: an endogenous mechanism for seizure termination.

ABSTRACT

MAIN PROBLEM: Epilepsy is one of the more common neurological disorders. The medication is often ineffective to the patients suffering from intractable temporal lobe epilepsy (TLE). As their seizures are usually self-terminated, the elucidation of the mechanism underlying endogenous seizure termination will help to find a new strategy for epilepsy treatment. We aim to examine the role of inhibitory interneurons in endogenous seizure termination in TLE patients. METHODS: Whole-cell recordings were conducted on inhibitory interneurons in seizure-onset cortices of intractable TLE patients and the temporal lobe cortices of nonseizure individuals. The intrinsic property of the inhibitory interneurons and the strength of their GABAergic synaptic outputs were measured. The quantitative data were introduced into the computer-simulated neuronal networks to figure out a role of these inhibitory units in the seizure termination. RESULTS: In addition to functional downregulation, a portion of inhibitory interneurons in seizure-onset cortices were upregulated in encoding the spikes and controlling their postsynaptic neurons. A patch-like upregulation of inhibitory neurons in the local network facilitated seizure termination. The upregulations of both inhibitory neurons and their output synapses synergistically shortened seizure duration, attenuated seizure strength, and terminated seizure propagation. CONCLUSION: Automatic seizure termination is likely due to the fact that a portion of the inhibitory neurons and synapses are upregulated in the seizure-onset cortices. This mechanism may create novel therapeutic strategies to treat intractable epilepsy, such as the simultaneous upregulation of cortical inhibitory neurons and their output synapses.