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Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells

Abstract

THE hippocampus is particularly vulnerable to a variety of conditions, such as anoxia, status epilepticus and senile dementia, in which central neurones are lost1,2. Most commonly, the lesion involves only the Sommer sector (h1) and the endfolium (h3–h5), sparing area h2, the fascia dentata and most regions outside the hippocampal formation. The consequences for hippocampal connections are unknown. Studies on the rat hippocampus suggest that connections made by the affected neurones could be replaced by axons of other neurones which project to the same areas3,4. These anomalous synapses might either compensate in part for the loss of cells or contribute to whatever functional deficits may derive from the lesion. Since a good deal is known about afferent and efferent hippocampal connections in the rat, this animal might serve as a model for studies of hippocampal damage. However, the selective pathology seen clinically cannot be reproduced by conventional lesioning techniques. Ideally, one would like to use a toxin relatively specific for the neurones in question. Kainic acid, a potent excitatory analogue of glutamic acid5–7, has been used to destroy neurones in the arcuate nucleus8 and striatum,9–11 while sparing fibres which pass to or through these regions. Previous workers have also briefly noted lesions in the hippocampus,8,11 but these were not described. Accordingly, we injected kainic acid intraventricularly into the rat brain and studied its effect on hippocampal neurones. We now report the unusual sensitivity of CA3–CA4, and to a lesser extent CA1, pyramidal cells to this agent. Our results suggest that kainic acid lesions can provide a model of hippocampal damage in man.

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NADLER, J., PERRY, B. & COTMAN, C. Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature 271, 676–677 (1978). https://doi.org/10.1038/271676a0

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