Changes in excitatory and inhibitory circuits of the rat hippocampus 12–14 months after complete forebrain ischemia
Section snippets
Animals and surgical procedures
The experiments were carried out in 25 adult (180–200 g) male Wistar rats (Charles–River, Budapest). All procedures followed those licensed by the Animal Research Ethics Committee of the Institute. All efforts were made to minimize animal suffering, and to reduce the number of animals used. The animals were anaesthetized with Equithesin (chlornembutal, 0.3 ml/100 g, i.p.), and the vertebral arteries were exposed by drilling the alar foramina bilaterally, then cauterized and split under direct
Results
Three groups of animals have been distinguished on the basis of the general pattern and degree of cell death in the hippocampus:
Group A. A nearly complete pyramidal cell loss has been observed in the dorsal CA1 region leading to an approximately 50% shrinkage in the height of the subfield, accompanied by immunocytochemical alterations (Fig. 1).
Group B. A thinner but surviving stratum pyramidale is the characteristic of these animals, indicating a partial pyramidal cell loss in the CA1 region.
Discussion
The main findings of this study are the following: (i) the local and extrinsic excitatory circuits of the hippocampus remain largely intact even a year after the ischemic insult; (ii) no sprouting of these pathways has been observed to any atopic regions or layers; and (iii) spiny interneurons selectively involved in feedback inhibition in the dentate gyrus and feedforward inhibition in the CA3 region are permanently lost 12–14 months after the ischemic challenge.
Ischemic animals were grouped
Conclusion
In the present study, we found that the main local and extrinsic excitatory pathways of the hippocampus do not show major qualitative alterations in their termination pattern. The loss of spiny interneurons in the hilus and in stratum lucidum is permanent, involves the entire population, and consequently most of the filopodiae on mossy terminals are lost 12–14 months after complete forebrain ischemia. These data suggest that feedback inhibition in the dentate gyrus and feedforward inhibition in
Acknowledgements
The authors are grateful to Drs K. G. Baimbridge, J. H. Rogers, R. Shigemoto, and T. Görcs for the gifts of antisera against parvalbumin, calbindin, calretinin, substance P receptor and metabotropic glutamate receptor 1α, respectively. The contribution of Dr C. Dolorfo at earlier stages of the experiments, the helpful discussions of Dr Péter Rajna and the excellent technical assistance of Ms E. Borók and Mr Gy. Goda is also gratefully acknowledged. This study was supported by the Howard Hughes
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