title: Development of epileptiform excitability in the deep entorhinal cortex after status epilepticus.
abstract: Epileptiform neuronal activity during seizures is observed in many brain areas, but its origins following status epilepticus (SE) are unclear. We have used the Li low-dose pilocarpine rat model of temporal lobe epilepsy to examine early development of epileptiform activity in the deep entorhinal cortex (EC). We show that during the 3-week latent period that follows SE, an increasing percentage of neurons in EC layer 5 respond to a single synaptic stimulus with polysynaptic burst depolarizations. This change is paralleled by a progressive depolarizing shift of the inhibitory postsynaptic potential reversal potential in layer 5 neurons, apparently caused by upregulation of the Cl(-) inward transporter NKCC1 and concurrent downregulation of the Cl(-) outward transporter KCC2, both changes favoring intracellular Cl(-) accumulation. Inhibiting Cl(-) uptake in the latent period restored more negative GABAergic reversal potentials and eliminated polysynaptic bursts. The changes in the Cl(-) transporters were highly specific to the deep EC. They did not occur in layers 1-3, perirhinal cortex, subiculum or dentate gyrus during this period. We propose that the changes in Cl(-) homeostasis facilitate hyperexcitability in the deep entorhinal cortex leading to epileptiform discharge there, which subsequently affects downstream cortical regions.
authors: Department of Neurosurgery, University of New Mexico School of Medicine, University of New Mexico, Albuquerque, NM, USA.
authors: Denis E
authors: DE
authors: Bragin
authors: Jennifer L
authors: JL
authors: Sanderson
authors: Steven
authors: S
authors: Peterson
authors: John A
authors: JA
authors: Connor
authors: Wolfgang S
authors: WS
authors: Müller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D004569:Electroencephalography; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000378:metabolism / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010862:Pilocarpine / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D055366:Synaptic Potentials / Q000502:physiology*; D013997:Time Factors; D000096922:K Cl- Cotransporters
chemical_list: D010862:Pilocarpine; D012333:RNA, Messenger; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters; C578879:Slc12a2 protein, rat