Transplantation and restoration of functional synapses between an identified neuron and its targets in the intact brain of Lymnaea stagnalis.
Most information available to date regarding the cellular and synaptic mechanisms of target cell selection and specific synapse formation has primarily come from in vitro cell culture studies. Whether fundamental mechanisms of synapse formation revealed through in vitro studies are similar to those occurring in vivo has not yet been determined. Taking advantage of the regenerative capabilities of adult molluscan neurons, we demonstrate that when transplanted into the host ganglia an identified neuron reestablishes its synaptic connections with appropriate targets in vivo. This synaptogenesis, however, was possible only if the targets were denervated from the host cell. Specifically, the giant dopamine neuron right pedal dorsal 1 (RPeD1) located in the pedal ganglia was isolated from a donor brain and transplanted into the visceral ganglia of the recipient brain. We discovered that within 2-4 days the transplanted RPeD1 exhibited extensive regeneration. However, simultaneous intracellular recordings failed to reveal synapses between the transplanted cell and its targets in the visceral ganglia, despite physical overlap between the neurites. To test whether the failure of a transplanted cell to innervate its target was due to the fact that the targets continued to receive input from the native RPeD1, the latter soma was surgically removed prior to the transplantation of RPeD1. Even after the removal of host soma, the transplanted RPeD1 failed to innervate the targets such as visceral dorsal 4 (VD4)-despite extensive regeneration by the transplanted cell. However, when RPeD1 axon was allowed to degenerate completely, the transplanted RPeD1 successfully innervated all of its targets and these synapses were similar to those seen between host RPeD1 and its targets. Taken together, our data demonstrate that the transplanted cells will innervate their potential targets only if the targets were denervated from the host cell. These data also lend support to the idea that, irrespective of their physical location in the brain, the displaced neurons are able to regenerate, recognize their targets, and establish specific synapses in the nervous system.
Lee
Thomas K M
TK
Department of Cell Biology and Anatomy, Respiratory and Neuroscience Research Groups, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Syed
Naweed I
NI
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000502:physiology; D016380:Brain Tissue Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004594:Electrophysiology; D017952:Ganglia, Invertebrate; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000378:metabolism; D008195:Lymnaea; D008564:Membrane Potentials; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D020127:Recovery of Function; D013569:Synapses / Q000502:physiology*
D007546:Isoquinolines; C017475:lucifer yellow