Engineering new synaptic connections in the C. elegans connectome

Most of what we currently know about how neural circuits work we owe to methods based on the electrical or optical recording of neural activity. This is changing dramatically. First, the advent of optogenetic techinques has enabled precise manipulation of the activity of specific neurons. Second, the development of super-resolution methods for obtaining detailed maps of synaptic connectivity has paved the way for uncovering the connectomes of entire brains or brain regions. We describe a third and complementary new strategy for investigating and manipulating neural circuits: the artificial insertion of new synapses into existing neural circuits using genetic engineering tools. We have successfully accomplished this in C. elegans. Thus, In addition to being the first animal with an entirely mapped connectome, C. elegans is now also the first animal to have an editable connectome. Variations on this approach may be applicable in more complex nervous systems.