Recurrent mossy fiber pathway in XXXX dentate gyrus: synaptic currents evoked in presence and absence of @entity410 -induced growth.

@entity410 @entity1024 @entity2134 @entity4176 @entity1315 @entity302 @entity140 @entity143 @entity35 @entity159
A common feature of @entity1315 and of animal models of @entity302 is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory feedback to these neurons that could facilitate @entity410 discharge. We used the @entity2134 model of @entity1315 to study the synaptic responses evoked by activating this pathway. Whole cell patch-clamp recording demonstrated that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic current (EPSC) in approximately 74% of granule cells from @entity35 that had survived >10 wk after @entity2134 -induced @entity159 . Recurrent mossy fiber growth was demonstrated with the Timm stain in all instances. In contrast, antidromic stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells studied 4-6 days after @entity159 , before recurrent mossy fiber growth became detectable. Notably, antidromic mossy fiber stimulation also evoked an EPSC in many granule cells from control @entity35 . Clusters of mossy fiber-like Timm staining normally were present in the inner third of the dentate molecular layer at the level of the hippocampal formation from which slices were prepared, and several considerations suggested that the recorded EPSCs depended mainly on activation of recurrent mossy fibers rather than associational fibers. In both @entity159 and control groups, the antidromically evoked EPSC was glutamatergic and involved the activation of both @entity140 / @entity4176 and @entity1024 ( @entity143 ) receptors. EPSCs recorded in granule cells from @entity35 with recurrent mossy fiber growth differed in three respects from those recorded in control granule cells: they were much more frequently evoked, a number of them were unusually large, and the @entity143 component of the response was generally much more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by stimulation of the perforant path appeared to be unaffected by a prior episode of @entity159 . These results support the hypothesis that recurrent mossy fiber growth and synapse formation increases the excitatory drive to dentate granule cells and thus facilitates repetitive synchronous discharge. Activation of @entity143 receptors in the recurrent pathway may contribute to @entity410 propagation under depolarizing conditions. Mossy fiber-granule cell synapses also are present in normal @entity35 , where they may contribute to repetitive granule cell discharge in regions of the dentate gyrus where their numbers are significant.
