DIFFERENTIAL NPY MESSENGER-RNA EXPRESSION IN GRANULE CELLS AND INTERNEURONS OF THE RAT DENTATE GYRUS AFTER KAINIC ACID INJECTION

Using in situ hybridization histochemistry neuropeptide Y (NPY) mRNA expression was investigated after intraperitoneal injection of kainic acid (KA) and after local application of KA or quinolinic acid into the dentate gyrus of the rat. Enhanced concentrations of NPY. mRNA were observed in interneurons of the hilus, including presumptive fusiform neurons and pyramidal-shaped basket cells already 4 hours after initiation of limbic seizures by KA (10 mg/kg, i.p.). Increased NPY expression persisted in neurons resistant to seizure-induced cell death (6-48 h after i.p. KA). Exceptionally high hybridization signals were found in interneurons of the hilus and the CA1 and CA3 sectors 8 months after KA-induced limbic seizures. In the granule cell layer only a transient but pronounced increase in NPY mRNA was observed 12-24 h after injection. Only moderate changes were observed in this cell layer at later intervals. Anticonvulsant treatment with thiopental, after a brief period of generalized seizures, prevented the increase in NPY mRNA in granule cells but not in interneurons. No change in NPY message was found also in granule cells of rats which responded with mild ''wet dog shake'' behavior but not with motor seizures to KA injection. Local injections of low doses of KA (0.05-0.2 nmol) or quinolinic acid (65-100 nmol) into the dentate gyrus of the hippocampus under deep thiopental anesthesia, after 24 h, resulted in increased concentrations of NPY message in interneurons of the ipsilateral, but not of the contralateral hilus and not in granule cells. Higher doses of the excitatory amino acid analogs caused partial neurodegeneration at the injection site, but enhanced NPY expression in interneurons of the contralateral dentate. Only the highest dose of quinolinic acid (100 nmol), resulting in general neuronal cell loss at the injection area, induced enhanced NPY mRNA expression also in granule cells of the contralateral dentate gyrus. The experiments suggest different mechanisms for NPY mRNA expression in interneurons and in granule cells of the dentate gyrus. Whereas in the stratum granulosum NPY mRNA expression was only observed after generalized limbic seizures, in hilar interneurons it was augmented by only moderate neuronal stimulation or directly by KA. (c) 1994 Wiley-Liss, Inc.