Российская академия наук


DEVELOPMENT OF SYNAPTIC INTERACTIONS BETWEEN GRAFTED AND HOST BRAIN NEURONS



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DEVELOPMENT OF SYNAPTIC INTERACTIONS BETWEEN GRAFTED AND HOST BRAIN NEURONS

Zhuravleva Z.N., Ermakov A.A., Ivashkina L.I., Karanov A.M.

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; Pushchino, Russia; zhuravleva@iteb.ru


A major goal of neurotransplantation is to reconstruct the damage neuronal circuits. It is known, that grafted neurons develop efferent projections to both appropriate and inappropriate host targets. Structural and molecular mechanisms underlying synaptic wiring are one of the most important topics. In this work, we used fragments of fetal dentate fascia tissue as donor materials for heterotransplantation into the primary somatosensory neocortex of the adult male rats. Five months postgrafting, the dentate fascia transplants and surrounding neocortex were investigated by electron microscopy. Synaptic endings of the dentate granule cell axons (mossy fibers) were identified by the well-known features: giant (up to 5 mkm) terminal boutons, multiple intraterminal

chemical active zones with the dendritic spines and significant adhesion junctions of the presynaptic boutons with the dendritic surfaces. For comparison, we also investigated the normal giant synapses in the hippocampal stratum lucidum.

Our findings showed that precursor cells differentiated into a range of neural and glial cell types in a tissue-specific fashion, as well as established the intercellular functional interactions within fascia dentate grafts. In the surrounding neocortex, synaptic endings of the mossy fibers mostly terminated on different dendritic segments and made both intraterminal active zones and symmetric adhesion junctions with the dendritic shafts. Presynaptic giant boutons of the ectopic mossy fiber synapses, as well as in norm, contained two types of synaptic vesicles: glutamatergic small clear vesicles and peptidergic large dense-core granules. However, comparative quantitative analysis showed that ectopic endings have far more neuropeptide granules than normal ones. Besides, there was considerable increasing in the number synaptic active zones accumulating peptidergic vesicles. The adhesion junctions between giant boutons and neocortical dendritic trunks were more numerous and extensive also. It is assumed, that neuropeptide co-transmitters and adhesive junctions promote adaptive crosstalk between the presynaptic terminals of ingrowing from graft mossy fibers and postsynaptic partners in host neocortical. This facilitates synaptic interactions of the dentate fascia grafts with non-specific neuronal targets in host brain. Thus, our findings give evidence that there are synaptogenic factors governing the synaptic communication after transplantation.


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