title: A portion of inhibitory neurons in human temporal lobe epilepsy are functionally upregulated: an endogenous mechanism for seizure termination.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key lab for Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.forename: Hao
authors.initials: H
authors.lastname: Qian
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Rong-Jing
authors.initials: RJ
authors.lastname: Ge
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Cui
authors.forename: Ru-Yuan
authors.initials: RY
authors.lastname: Zhu
authors.forename: Long-Sheng
authors.initials: LS
authors.lastname: Pan
authors.forename: Zhi-Pei
authors.initials: ZP
authors.lastname: Lin
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000927:Anticonvulsants / Q000494:pharmacology; D001703:Biophysics; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D003198:Computer Simulation; D015536:Down-Regulation / Q000187:drug effects; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D055366:Synaptic Potentials / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; C070614:neurobiotin; D014635:Valproic Acid; D001710:Biotin
keywords: Epilepsy; Excitability; GABA; Human brain; Neuron; Synaptic transmission