Outgrowth-promoting molecules in the adult hippocampus after perforant path lesion

Lesion-induced neuronal plasticity in the adult central nervous system of h igher vertebrates appears to be controlled by region- and layer-specific mo lecules. In this study we demonstrate that membrane-bound hippocampal outgr owth-promoting molecules, as present during the development of the entorhin o-hippocampal system and absent or masked in the adult hippocampus, appear 10 days after transection of the perforant pathway. We used an outgrowth pr eference assay to analyse the outgrowth preference of axons from postnatal entorhinal explants on alternating membrane lanes obtained from hippocampus deafferented from its entorhinal input taken 4, 10, 20, 30 and 80 days pos t-lesion and from adult control hippocampus. Neurites from the entorhinal c ortex preferred to extend axons on hippocampal membranes disconnected from their entorhinal input for 10 days in comparison with membranes obtained fr om unlesioned adult animals. Membranes obtained from hippocampi disconnecte d from their entorhinal input for 10 days were equally as attractive for gr owing entorhinal cortex (EC) axons as membranes from early postnatal hippoc ampi. Further analysis of membrane properties in an outgrowth length assay showed that entorhinal axons extended significantly longer on stripes of le sioned hippocampal membranes in comparison with unlesioned hippocampal memb ranes. This effect was most prominent 10 days after lesion, a time point at which axonal sprouting and reactive synaptogenesis are at their peak. Phos pholipase treatment of membranes obtained from unlesioned hippocampi of adu lt animals strongly promoted the outgrowth length of entorhinal axons on th ese membranes but did not affect their outgrowth preference for deafferente d hippocampal membranes. Our results indicate that membrane-bound outgrowth -promoting molecules are reactivated in the adult hippocampus following tra nsection of the perforant pathway, and that neonatal entorhinal axons are a ble to respond to these molecules. These findings support the hypothesis of a temporal accessibility of membrane-bound factors governing the layer-spe cific sprouting of remaining axons following perforant path lesion in vivo.