Acute dendrotoxic changes in the hippocampus of kainate treated rats

Kainic acid (KA), a potent neuroexcitatory and neurotoxic analog of glutamate (Glu), induces a widespread pattern of brain damage when administered subcutaneously to adult rats. The hippocampus is among the brain regions most consistently and severely damaged. Here we describe acute swelling of certain spines and branchlets of dendrites as the first detectable sign of KA neurotoxic changes in the hippocampus. These swellings conform to a laminar pattern suggesting selective toxic interaction of KA at specific levels of the dendritic trees of hippocampal pyramidal and dentate granule neurons. The frequency and severity of involvement of each type of hippocampal neuron at each level of its dendritic tree was roughly estimated and neuronal types were ranked from the most to least extensively involved (CA3 greater than CA4 greater than CA1 greater than CA2 greater than dentate granules). The same rank order has been described for the vulnerability of these neurons to acute destruction following intraventricular KA administration. Because the pattern of dendritic dilatations observed corresponds well with the pattern of termination of putative glutamergic inputs to the hippocampus, we interpret the findings as being consistent with the hypothesis that the toxic effects of KA are mediated through glutamergic excitatory receptors. We propose that the sensitivity of a given neuron to the neurodestructive action of KA may be determined by the percentage of its dendritic surface occupied by Glu receptors. We suspect that most, if not all, hippocampal neurons receive some glutamergic input and, therefore, are sensitive to KA. That CA3 pyramids are substantially more sensitive than dentate granules may signify that the former receive many more Glu terminals than the latter, an assumption quite consistent with our observation that focal dendritic swellings were both more densely and more widely distributed over the dendritic surfaces of the former than the latter.