Development of epileptiform excitability in the deep entorhinal cortex after status epilepticus.
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.
Bragin
Denis E
DE
Department of Neurosurgery, University of New Mexico School of Medicine, University of New Mexico, Albuquerque, NM, USA.
Sanderson
Jennifer L
JL
Peterson
Steven
S
Connor
John A
JA
Müller
Wolfgang S
WS
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
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