Highly specific neuron loss preserves lateral inhibitory circuits in the dentate gyrus of kainate-induced epileptic rats

Patients with temporal lobe epilepsy display neuron loss in the hilus of th e dentate gyrus. This has been proposed to be epileptogenic by a variety of different mechanisms. The present study examines the specificity and exten t of neuron loss in the dentate gyrus of kainate-treated rats, a model of t emporal lobe epilepsy. Kainate-treated rats lose an average of 52% of their GAD-negative hilar neurons (putative mossy cells) and 13% of their GAD-pos itive cells (GABAergic interneurons) in the dentate gyrus. Interneuron loss is remarkably specific; 83% of the missing GAD-positive neurons are somato statin-immunoreactive. Of the total neuron loss in the hilus, 97% is attrib uted to two cell types-mossy cells and somatostatinergic interneurons. The retrograde tracer wheat germ agglutinin (WGA)-apoHRP-gold was used to ident ify neurons with appropriate axon projections for generating lateral inhibi tion. Previously, it was shown that lateral inhibition between regions sepa rated by 1 mm persists in the dentate gyrus of kainate-treated rats with hi lar neuron loss. Retrogradely labeled GABAergic interneurons are found cons istently in sections extending 1 mm septotemporally from the tracer injecti on site in control and kainate-treated rats. Retrogradely labeled putative mossy cells are found up to 4 mm from the injection site, but kainate-treat ed rats have fewer than controls, and in several kainate-treated rats virtu ally all of these cells are missing. These findings support hypotheses of t emporal lobe epileptogenesis that involve mossy cell and somatostatinergic neuron loss and suggest that lateral inhibition in the dentate gyrus does n ot require mossy cells but, instead, may be generated directly by GABAergic interneurons.