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J Physiol Volume 569, Number 3, 833-847, December 15, 2005 DOI: 10.1113/jphysiol.2005.094599
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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, 105 boulevard de l'Hôpital, Paris 75013, France
2 INSERM U497, Ecole Normale Superieure, 46 rue d'Ulm, Paris 75005, France

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 depolarized to a potential at which action potentials were no longer evoked. No further activity was detected near the injection site for 3–5 h. In longitudinal slices of the CA3 region, firing induced by KA injection spread at a velocity close to 1 x 104 mm ms1. The velocity increased to ~1 x 101 mm ms1 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 h after injection. We also examined slices prepared from animals injected with KA, at a delay of 2–5 h 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.

(Received 27 July 2005; accepted after revision 18 October 2005; first published online 20 October 2005)
Corresponding author R. Miles: INSERM U739, CHU Pitié-Salpêtrière, 105 boulevard de l'Hôpital, 75013 Paris, France. Email: rmiles{at}chups.jussieu.fr




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C. Le Duigou, V. Bouilleret, and R. Miles
Epileptiform activities in slices of hippocampus from mice after intra-hippocampal injection of kainic acid
J. Physiol., October 15, 2008; 586(20): 4891 - 4904.
[Abstract] [Full Text] [PDF]




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