title: Changes in mIPSCs and sIPSCs after kainate treatment: evidence for loss of inhibitory input to dentate granule cells and possible compensatory responses.
abstract: How inhibition is altered after status epilepticus and the role of inhibition during epileptogenesis remain unsettled issues. The present study examined acute (4-7 days) and chronic (>3 mo) changes of GABA(A) receptor-mediated inhibitory synaptic input to dentate granule cells after kainate-induced status epilepticus. Whole cell patch-clamp techniques were used to record spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in the presence of 6,7-dinitroquinoxaline-2,3-dione and dl-2-amino-5-phosphonopentanoic acid to block glutamatergic excitatory synaptic transmission. In both groups, mean sIPSC frequency of dentate granule cells from the saline- and kainate-treated rats was not significantly different. However, mIPSC frequency from the kainate-treated rats of both groups was approximately 30% lower than that of the respective saline controls. The mean amplitude of sIPSCs and mIPSCs from kainate-treated rats was not reduced in either the acute or chronic groups. The mean 10-90% rise time of IPSCs was not altered in kainate-treated rats, but the decay time constant was slightly longer than in controls, and the charge transfer 4-7 days after kainate treatment was significantly larger. The similar reduction of mIPSC frequency (i.e., approximately 30%) in the two groups of kainate-treated rats suggests a decreased inhibitory input to dentate granule cells (presumably due to a partial loss of inhibitory interneurons that innervate them) without recovery during epileptogenesis. The lack of effect on sIPSC frequency and the decreased mIPSC frequency in both groups suggests a possible compensatory increase in firing rate of interneurons, which may involve a hypothetical reduction of inhibitory input to the remaining interneurons.
authors.affiliation: Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Shao
authors.forename: F Edward
authors.initials: FE
authors.lastname: Dudek
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology*; D004347:Drug Interactions; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D013779:Tetrodotoxin; D007608:Kainic Acid; D001640:Bicuculline