Alterations of perisomatic GABA synapses on hippocampal CA1 inhibitory interneurons and pyramidal cells in the kainate model of epilepsy
Section snippets
Experimental procedures
For kainate lesions, male Sprague–Dawley rats (Charles River, Montre ́al, Que ́bec, Canada; n=4) were injected intracerebroventricularly with kainate.38., 41. Briefly, adult rats (150–160 g) were anesthetized with ketamine (165 mg/kg, i.m.), xylazine (10 mg/kg, i.m.) and atropine (0.27 mg/kg, i.p.). Rats were positioned in a stereotaxic apparatus and bilateral intracerebroventricular injections of kainate (0.55 μg/μl, 0.9% saline, pH 7.3–7.4) were made using a 10-μl Hamilton syringe. Stereotaxic
GABA and non-GABA synaptic contacts on interneurons and pyramidal cells
Postembedding GABA immunogold labeling was used to identify pyramidal cells and interneurons in the hippocampal CA1 region. GABA-immunonegative cells with a pyramidal-shaped soma located in the stratum pyramidale were identified as pyramidal cells, whereas GABA-immunopositive cells with a soma located either in the O/A or LM were selected as two groups of interneurons. In general, cells found in the O/A and LM were GABA immunopositive. GABA-immunonegative neurons in the O/A or LM were not
Discussion
Electron microscopy and postembedding immunogold staining for GABA were used (i) to characterize perisomatic GABA and non-GABA synaptic contacts on CA1 pyramidal cells and inhibitory interneurons located in the O/A and LM of normal rats, and (ii) to examine if these synaptic contacts were altered in the chronic hyperexcitable hippocampus following kainate treatment. In normal animals, our main findings were that the number and total length of perisomatic GABA synapses were significantly smaller
Conclusions
Using postembedding immunogold labeling for GABA and electron microscopy, we found that the number and total length of perisomatic GABA and non-GABA synaptic contacts were significantly different between O/A, LM and pyramidal cells in normal animals. Our results suggest that LM interneurons receive less perisomatic GABAergic innervation than O/A interneurons and pyramidal cells. In addition, O/A interneurons were preferentially innervated by perisomatic non-GABA inputs compared to LM
Acknowledgements
This work was supported by the Fonds de la Recherche en Santé du Québec (FRSQ; J.-C.L.), the Medical Research Council of Canada (MRCC; J.-C.L. and C.B.), the Savoy Foundation (F.M.), a Research Center grant from the Fonds pour la Formation de Chercheurs et l'Aide à la Recherche (FCAR) to the Groupe de Recherche sur le Système Nerveux Central and an Équipe de Recherche grant from the FCAR (J.-C.L.).
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