title: Enhancement of asynchronous release from fast-spiking interneuron in human and rat epileptic neocortex.
abstract: Down-regulation of GABAergic inhibition may result in the generation of epileptiform activities. Besides spike-triggered synchronous GABA release, changes in asynchronous release (AR) following high-frequency discharges may further regulate epileptiform activities. In brain slices obtained from surgically removed human neocortical tissues of patients with intractable epilepsy and brain tumor, we found that AR occurred at GABAergic output synapses of fast-spiking (FS) neurons and its strength depended on the type of connections, with FS autapses showing the strongest AR. In addition, we found that AR depended on residual Ca²⁺ at presynaptic terminals but was independent of postsynaptic firing. Furthermore, AR at FS autapses was markedly elevated in human epileptic tissue as compared to non-epileptic tissue. In a rat model of epilepsy, we found similar elevation of AR at both FS autapses and synapses onto excitatory neurons. Further experiments and analysis showed that AR elevation in epileptic tissue may result from an increase in action potential amplitude in the FS neurons and elevation of residual Ca²⁺ concentration. Together, these results revealed that GABAergic AR occurred at both human and rat neocortex, and its elevation in epileptic tissue may contribute to the regulation of epileptiform activities.
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
authors.forename: Mingpo
authors.initials: M
authors.lastname: Yang
authors.forename: Cuiping
authors.initials: C
authors.lastname: Tian
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Wang
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D055724:Electrophysiological Phenomena; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000008:administration & dosage / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; D002118:Calcium