In Vivo Regeneration and Synaptic Connectivity

In contrast with vertebrate and other invertebrate species (Drosophila and C. elegans) where the mechanisms underlying specific synapse formation are generally investigated in developing animals, the adult mollusks with their inherent regenerative capacity are most favored for similar studies. Behaviorally defined, injured neurons from a variety of molluscan species such as Melampus7, Lymnaea 8 (Figure 2.1A; Colorplate 2) Helisoma9'10, and Aplysia11 have been shown to regenerate their axonal projections, not only in vitro, but also in the intact animals. In most instances, regeneration from injured central neurons is complete and results in functional recovery7. However, the mechanisms underlying specific synapse formation could still not be elucidated in these intact preparations, due mainly to the intricacies of the intact brain and the lack of knowledge regarding various intrinsic and extrinsic factors that facilitate synapse formation in vivo. A variety of in vitro cell culture techniques were thus developed that enabled the extraction of uniquely identifiable neurons from the CNS/central ring ganglia. These approaches have since revealed that individually isolated neurons not only regenerate their neuritic processes in cell culture, but also develop specific synapses which are similar to those seen in vivo. This innate propensity of molluscan neurons to reconnect in vitro has enabled a number of laboratories to define various steps and mechanisms underlying synapse formation.

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