RESTORATION OF MOSSY FIBER PROJECTION IN SLICE COCULTURES OF DISLOCATED DENTATE GYRUS AND DEGRANULATED HIPPOCAMPUS

Regional specificity of the messy fiber projection is a well described feature of hippocampal intrinsic connectivity. Possible mechanisms in volved in the formation of this specific projection include attraction molecules localized in the target area or repulsive cues preventing f rom ingrowth in non-target areas. To test this hypothesis, using organ otypic co-cultures of dentate gyrus and irradiated degranulated hippoc ampal slices, we have disrupted the pathway normally taken by messy fi bers. The dentate gyrus explant was ectopically placed facing the alve us/stratum oriens of the irradiated hippocampal slice forcing the mess y fibers to cross the stratum oriens to reach their target area. Exten sive plexuses of labeled messy fibers were observed in the hilus and a djacent pyramidal cell layer of non-irradiated dentate gyrus explants. A few messy fibers crossed the border between the co-cultures and rea ched their specific termination area in the irradiated hippocampus whe re they formed characteristic multiple synaptic contacts on their targ et cells. In addition to messy fibers, numerous thin and varicose non- mossy fibers invade all parts of the co-cultured hippocampus establish ing symmetric as well as asymmetric synapses. From these data we assum e that messy fiber axons emerging from dislocated non-irradiated denta te gyrus explants find their normal termination zone in the co-culture d degranulated hippocampal slice even if they are forced to run an unu sual pathway. These results support the idea that an attraction signal arising from the target area is involved in the formation of this spe cific projection.