Understanding neural circuit function through synaptic engineering

Synapses are a key component of neural circuits, facilitating rapid and specific signalling between neurons. Synaptic engineering — the synthetic insertion of new synaptic connections into in vivo neural circuits — is an emerging approach for neural circuit interrogation. This approach is especially powerful for establishing causality in neural circuit structure–function relationships, for emulating synaptic plasticity and for exploring novel patterns of circuit connectivity. Contrary to other approaches for neural circuit manipulation, synaptic engineering targets specific connections between neurons and functions autonomously with no user-controlled external activation. Synaptic engineering has been successfully implemented in several systems and in different forms, including electrical synapses constructed from ectopically expressed connexin gap junction proteins, synthetic optical synapses composed of presynaptic photon-emitting luciferase coupled with postsynaptic light-gated channels, and artificial neuropeptide signalling pathways. This Perspective describes these different methods and how they have been applied, and examines how the field may advance. Synaptic engineering involves the synthetic insertion of new synapses between neurons in vivo. In this Perspective, Rabinowitch, Colón-Ramos and Krieg explore this emerging approach for studying neural circuits, describing the different methods that have been used and how they have been implemented.