In Vivo Synapse Formation and Behavioral Recovery Following Single Cell Transplantation

It can always be argued that the in vitro approach only offers an artificial environment, which bears little resemblance to the in vivo milieu that is pivotal for normal development. To determine whether the data obtained in vitro can be extrapolated to derive conclusions about fundamental principles governing synapse formation in vivo, single-cell transplantation techniques were developed in Lymnaea. Specifically, ablation of the single respiratory neuron VD4 in the intact animal rendered the snail unable to exhibit normal respiratory behavior55. This behavioral deficit was however restored by transplanting a VD4 neuron from a donor animal. The transplanted neuron subsequently recapitulated its pattern of synaptic connectivity and restored functional contacts with its target cells as well. Interestingly, when a VD4 was transplanted into the host in the presence of its native VD4, the newly transplanted cell failed to innervate its appropriate target and began making contacts with inappropriate target cells. These findings have been confirmed further by transplanting RPeDl into the right parietal ganglia56, a location that is different from its native habitat (right pedal ganglia). Consistent with our previous study, the transplanted neuron would only connect with its targets if they were deprived of synaptic input form the host cell. Together, these data suggest that the neuronal ability to regenerate and recognize appropriate target neurons in cell culture involves fundamental mechanisms that are likely operative in the intact brain.

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