Maintenance of synaptic positions and function

Although neuronal circuits of metazoans are largely established during embryogenesis, they persist throughout the lifetime. For example, in C. elegans, the circuitry is largely laid out in embryogenesis, but the nematode grows 100-fold in volume during its lifetime. This poses a major challenge regarding the maintenance of synaptic connections, the major communication structure between presynaptic neurons and postsynaptic target cells. How neurons cope with growth, maturation and mechanical stress to preserve the architecture of circuits is not well understood.

Using C. elegans interneuron AIY as a model, we discovered that cima-1 regulates AIY synaptic maintenance. In wild type juvenile or adult animals, AIY has three distinct anatomical regions along its neurite: a segment proximal to the AIY cell body that is devoid of synapses (zone 1); a dense presynaptic region just as the AIY process turns dorsally (zone 2); and a distal axon segment within the nerve ring that has about ten small presynaptic specializations (zone 3) (Fig. A, C, D, G). In cima-1 mutant animals, AIY presynaptic structure is wild type in larval stage (Fig. B). However, they form ectopic presynapses at the asynaptic zone 1 region when they reach adulthood, as assayed by presynaptic vesicle marker GFP::RAB-3 and presynaptic active zone marker SYD-1::GFP (Fig D, F, H). Mosaic analysis and tissue-specific expression data suggest that cima-1 functions non-cell-autonomously in epidermis to maintain AIY presynaptic pattern. Currently we are working toward to understanding the molecular and cellular mechanisms underlying cima-1 function(s).