Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 30, Issue 4, Pages 611-624Publisher
WILEY
DOI: 10.1111/j.1460-9568.2009.06863.x
Keywords
bumetanide; GABA; KCC2; Li-pilocarpine; NKCC1; rat
Categories
Funding
- NIH [AA015614, AA014127]
- NRSA [AA016880]
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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.
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