Comparative connectomics reveals mechanisms for synaptic specificity

Our nervous system is made of billions of neurons that process sensory information and control behavior. It is delicately organized into circuits with specifically tuned cell-to-cell connections that are essential for proper function. During development, neurons project to remote locations in search of their synaptic partners. Surrounded by numerous cells along their trajectory, these developing neurons are challenged to connect only with a specific set of cells. But how do neural circuits achieve such precise connectivity?

I study the assembly of a circuit for mechanosensation in Drosophila larva. I genetically manipulated the growth patterns of mechanosensory neurons to change their position in the central nervous system. Using electron microscopy, I reconstructed their morphology and mapped their synapses. I found that their partner neurons manage to connect to the mechanosensory cells at their new location by extending ectopic branches. Despite this compensation, the connectivity balance of the circuit is disturbed, resulting in a deficient mechanosensory behavior. Similarly, abolishing synaptic communication during development in these neurons results in a connectivity imbalance with long-lasting behavioral defects. These results suggest that partner-derived cues are sufficient for the recognition between specific partners and establishment of connections. However, without orderly positioning of axon terminals by positional cues and without synaptic activity during embryonic development, the number and strength of functional connections are altered with significant consequences for behavior. Thus, multiple mechanisms including global positional cues, partner-derived cues, and synaptic activity contribute to proper circuit assembly in the developing Drosophila nerve cord.