POSSIBLE FUNCTIONAL CONSEQUENCES OF SYNAPTIC REORGANIZATION IN THE DENTATE GYRUS OF KAINATE-TREATED RATS

The hypothesis that lesion-induced hippocampal granule cell axon sprou ting causes granule cell hyperexcitability was tested in the rat. Kain ic acid damaged dentate hilar neurons, decreased granule cell inhibiti on, and increased granule cell excitability to afferent stimulation, a ll before synaptic reorganization occurred. Granule cell recurrent inh ibition and relatively normal excitability were unexpectedly restored as granule cell axon sprouting occurred. Anatomical analysis revealed that a dense innervation of inhibitory neurons by aberrant granule cel l axons was a consistent feature in each animal. These results indicat e that granule cell hyperexcitability precedes dentate synaptic reorga nization and is associated with the selective interneuron loss that is the presumed stimulus for axon sprouting. Thus, if granule cell axon sprouting has functional significance, it may be primarily inhibitory, rather than epileptogenic, in nature.