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First published online on October 20, 2005.
Copyright © 2005 by The Physiological Society
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jphysiol.2005.094599v1
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Received July 27, 2005
Revised August 30, 2005
Accepted after revision October 18, 2005

Effects of focal injection of kainic acid into the mouse hippocampus in vitro and ex vivo

Caroline Le Duigou1, Lucia Wittner1, Lydia Danglot2, and Richard Miles1*

1 INSERM U739, CHU Pitié-Salpêtrière, UPMC
2 INSERM U497, ENS

* To whom correspondence should be addressed. E-mail: rmiles{at}chups.jussieu.fr.

Intra-hippocampal kainate injection induces an epileptiform activity termed status epilepticus. We examined the emergence of this activity with extracellular and intracellular records of responses 1) to focal kainate (KA) application in slices of mouse hippocampus and 2) of slices from mice injected with KA. The effects varied with distance from the injection site of KA. At distances less than ~800 µm, KA injection induced a strong increase in extracellular firing which ceased after 2-4 min. Pyramidal cells in this zone fired and depolarised to a potential at which action potentials were no longer evoked. No further activity was detected near the injection site for 3-5 hrs. In longitudinal slices of the CA3 region, firing induced by KA injection spread at a velocity close to 1x10-4 mm.ms-1. The velocity increased to ~1x10-1 mm.ms-1 when synaptic inhibition was blocked, suggesting that inhibitory processes normally restrict the spread of firing. At distances of 1.5-2.5 mm, KA injection induced a short-term increase in firing which was maintained, and often increased and rhythmic at gamma frequencies at 2-5 hrs after injection. We also examined slices prepared from animals injected with KA, at a delay of 2-5 hours corresponding to the expression of status epilepticus. Near the injection site, Gallyas silver staining revealed cellular degeneration and no activity was recorded. Interictal-like activity was generated by ipsilateral slices distant from KA injection. Contralateral slices also generated an interictal-like activity but no cell death was detected. Hippocampal oscillations generated at distant sites may be associated with status epilepticus.


Key words: Epilepsy • Hippocampus • Kainate







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