CHARACTERIZATION OF TARGET-CELLS FOR ABERRANT MOSSY FIBER COLLATERALSIN THE DENTATE GYRUS OF EPILEPTIC RAT

Previous studies have demonstrated formation of recurrent excitatory c ircuits between sprouted messy fibers and granule cell dendrites in th e inner molecular layer of the dentate gyrus (9, 28, 30). In addition, there is evidence that inhibitory nonprincipal cells also receive an input from sprouted messy fibers (39). This study was undertaken to fu rther characterize possible target cells for sprouted messy fibers, us ing immunofluorescent staining for different calcium-binding proteins in combination with Timm histochemical staining for messy fibers. Rats were injected intraperitoneally with kainic acid in order to induce e pileptic convulsions and messy fiber sprouting. After 2 months surviva l, hippocampal sections were immunostained for parvalbumin, calbindin D28k, or calretinin followed by Timm-staining. Under a fluorescent mic roscope, zinc-positive messy fibers in epileptic rats were found to su rround parvalbumin-containing neurons in the granule cell layer and to follow their dendrites, which extended toward the molecular layer. In addition, dendrites of calbindin D28k-containing cells were covered b y multiple messy fiber terminals in the inner molecular layer. However , the calretinin-containing cell bodies in the granule cell layer did not receive any contacts from the sprouted fibers. Electron microscopi c analysis revealed that typical Timm-positive messy fiber terminals e stablished several asymmetrical synapses with the soma and dendrites o f nonpyramidal cells within the granule cell layer. These results prov ide direct evidence that, in addition to recurrent excitatory connecti ons, inhibitory circuitries, especially those responsible for the peri somatic feedback inhibition, are formed as a result of messy fiber spr outing in experimental epilepsy. (C) 1997 Academic Press.