Trophic interactions, regeneration, and synaptic reorganization after prenatal intervention in the nervous system of the mouse
Description
The following experiments were designed to study interactions among developing neurons, especially tissue plasticity, axonal target selection, and trophic influences, in the nervous system of the developing mouse. Exo utero surgery techniques were utilized for altering the normal course of neural development using a variety of experimental paradigms. First, to study prenatal tissue plasticity, one-half of the undifferentiated retina was removed in the third trimester. Animals viewed at various postnatal timepoints showed that the embryonic mouse eye has a remarkable ability to heal and restore ocular integrity after severe trauma. In the second paradigm, these methods were used to study regional differentiation and projection outgrowth of cerebral cortical circuitry. The entorhinal region of the embryonic mouse cortex was localized with fluorescent dye labeling. Labeling also revealed a prenatal projection to the hippocampus which appears to be involved in regulating further postnatal innervation of this region. Finally, after locating the entorhinal primordium in the posterior temporal cortex, the identified cortical region was ablated prenatally, at embryonic day 16. Hippocampal target cells, the dentate gyrus granule cells, responded to prenatal deafferentation in two distinct ways. In some animals, deafferentation caused massive cell losses in the granule cell layer, which were later mirrored in the CA3 pyramidal cell layer. Other animals showed sprouting of granule cell axons into the open synaptic space in the molecular layer of the dentate at very late postnatal stages. Both sprouting and cellular degeneration indicate that deafferentation causes a disruption in trophic regulation between the entorhinal neuron and the dentate granule cell. Viewed together, these studies provide a first approach to questions concerning important capabilities and events that occur prenatally, but have a direct influence on postnatal development