4/27/2023 0 Comments Axon to dendrite![]() The migratory behavior of hippocampal axons was similar to that of the olivary axons ( Fig. As a whole, the interaction between inferior olivary axons and GC dendrites appeared to be random. ![]() Some of them crossed the granule cell dendrites, whereas others coursed along them. The inferior olivary axons ran in more complex fashions ( Movie S2). When they collided with granule cell dendrites, the growth cones simply crossed the dendrites, as if these axon tips were ignoring the latter. Growth cones of the pontine axons tended to migrate straight. In cultures at two to four div, we observed the initial processes of axon-dendrite attachment by live-cell imaging ( Fig. In these cocultures, the explants radially extended their EGFP-positive axons, whereas GCs developed multiple dendrites, as visualized by immunostaining for MAP-2 ( Fig. Results Initial Processes of Axon–Dendrite Association. Our results show that the GC dendrites can indeed discriminate their real partners from others even in vitro. Here, we tested whether the GCs could distinguish between the mossy fibers and other axons for synaptogenesis in in vitro cultures. In fact, these fibers do form transient synapses with the respective inappropriate partners ( 14), although these synapses are abandoned with maturation. During development, these two classes of fibers are spatially able to touch inappropriate partners, that is, the mossy fibers contacting Purkinje cells and the climbing fibers, GCs. On the other hand, the climbing fibers, derived from the inferior olivary nuclei, selectively associate with Purkinje cells for synaptogenesis ( 2). The dendrites of the GCs are connected to the mossy fibers, assuming a characteristic claw-like morphology at their distal ends and organizing synaptic glomeruli ( 11– 13). The mossy fibers, the major sources of which are the pontine nuclei, form synapses with cerebellar granule cells (GCs). The major afferent axons in the cerebellum are mossy and climbing fibers. To this end, we used neurons involved in the formation of the cerebellar circuitries ( Fig. In the present study, we re-examined whether synaptogenesis is a nonselective process in vitro, seeking to determine whether neurons can still recognize their specific partners even under in vitro culture conditions. specific nature of synaptogenesis in their establishment of specific circuitries. The question then arises as to how neurons compromise the nonspecific vs. These observations suggest that synapses can be generated irrespective of the neuronal types combined, when appropriate molecular systems that can link the pre- and postsynaptic membranes are provided on the cellular surfaces. Nonneuronal cells, which have been engineered to express certain synaptic adhesion molecules ( 9, 10), can induce the accumulation of presynaptic proteins in axons when they contact one another. Clustering of presynaptic elements can be induced even by nonspecific polybasic substrates ( 8). For example, in cultures of isolated hippocampal pyramidal neurons, mismatching of presynaptic and postsynaptic components, such as the localization of GABA receptors at non-GABAergic terminals, can occur ( 7). This has particularly been observed in neurons cultured in vitro. These observations suggest that GC dendrites can select their authentic partners for synaptogenesis even in vitro, forming the synapses with a GC-specific nature only with them.ĭespite the apparent accuracy of the neuronal connectivities in the mature brain, it is thought that synaptogenesis during development is promiscuous ( 6). In the latter case, synaptic proteins could accumulate between axons and dendrites, but these synapses were randomly distributed throughout the contact sites, and also their synaptic vesicle recycling was anomalous. The GC neurons formed synapses with pontine axons predominantly at the distal ends of their dendrites, reproducing the characteristic morphology of their synapses observed in vivo, whereas they failed to do so when combined with other axons. We cocultured GC neurons with pontine or inferior olivary axons, the major sources for mossy and climbing fibers, respectively, as well as with hippocampal axons as a control. In the cerebellum, granule cell (GC) dendrites form synaptic connections specifically with mossy fibers, but not with climbing fibers. Here we reexamined whether neurons can or cannot select particular partners in vitro. However, it is also known that neurons promiscuously form synapses with nonspecific partners, in particular when cultured in vitro, causing controversies about neural recognition mechanisms. Neural circuits are generated by precisely ordered synaptic connections among neurons, and this process is thought to rely on the ability of neurons to recognize specific partners.
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