The mossy fibers (MFs) arising from dentate granule cells project primarily onto a narrow segment of the proximal dendrites of hippocampal @entity1400 pyramidal cells. The mechanisms underlying this specific MF target selection are not fully understood. To investigate the cellular basis for development of the stereotyped MF trajectories, we have arranged the fascia dentata and hippocampal Ammon's horn tissues in diverse topographical patterns in organotypic explant coculture systems. Here we show that cyclic @entity377 signaling pathways regulate the MF pathfinding. When the dentate gyrus explants were ectopically placed facing the @entity1400 stratum oriens of hippocampal slices, MFs crossed the border between cocultures and reached their appropriate target area in the Ammon's horn, as assessed by membrane tracer labeling, Timm staining, electrophysiological recording of synaptic responses, and optical analyses using a voltage-sensitive dye. This lamina-specific MF innervation was disrupted by pharmacological blockade of cGMP pathway. Similar apposition of the dentate grafts near the @entity1399 region of host slices rarely resulted in MF ingrowth into the Ammon's horn. Under blockade of @entity268 pathway, however, the MFs were capable of making allopatric synapses with @entity1399 neurons. These data were further supported by the pharmacological data obtained from granule cells dispersed over hippocampal slice cultures. Thus, our findings suggest that the stereotyped MF extension is mediated by at least two distinct factors, i.e., an attractant derived from the @entity1400 region and a repellent from the @entity1399 region. These factors may be regulated differently by @entity268 and @entity6708 signaling pathways.

Cyclic XXXX -mediated regulation of hippocampal mossy fiber development: a target-specific guidance.

@entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity1400 :: ('761', 'Gene') :: ['CA3'] @entity6708 :: ('CHEBI:16356', 'Chemical') :: ['cGMP'] @entity1399 :: ('759', 'Gene') :: ['CA1'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide']
@entity377 :: (CHEBI:36976,Chemical) :: ['nucleotide']
