Repair of the entorhino-hippocampal projection in vitro.
The repair of axonal projections and the reconstruction of neuronal circuits after CNS lesions or during neurodegenerative disease are major challenges in restorative neuroscience. We have explored the potential of transplanted immature neurons to repair a specific axonal projection in an entorhino-hippocampal slice culture model system. When slices of immature entorhinal cortex (EC) from tau-GFP transgenic mice were cultured next to slices from postnatal hippocampus, an axonal projection from the E18 embryonic entorhinal cortex to the dentate gyrus of the postnatal hippocampus developed, which was similar to that observed in control cultures. Even more immature neuronal precursors in slices from E15 developing cerebral cortex differentiated and established an axonal projection to the hippocampal slice. This projection terminated specifically in the outer molecular layer of the dentate gyrus, the normal target area of the entorhino-hippocampal projection. When embryonic tissue from the presumptive brainstem area was used, there was still a subpopulation of fibers with a specific termination in the outer molecular layer, but few specific fibers were found in cocultures with embryonic midbrain. Our results show that very immature cortical neurons are potentially able to form an entorhino-hippocampal projection that terminates in a correct lamina-specific fashion in the dentate gyrus. These findings support the idea that immature neuronal precursor cells could be used for the reconstruction of specific neuronal circuits.
Radojevic
Vesna
V
Universität Basel, Anatomisches Institut, CH-4056 Basel, Switzerland.
Kapfhammer
Josef P
JP
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D001933:Brain Stem / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018728:Entorhinal Cortex / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D005333:Fetus; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D066298:In Vitro Techniques; D008164:Luminescent Proteins; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D019580:Perforant Pathway / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000648:ultrastructure; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D016875:tau Proteins; D049452:Green Fluorescent Proteins