Axon–axon interactions determine modality-specific wiring and subcellular synaptic specificity in a somatosensory circuit

Synaptic connections between neurons are often formed in precise subcellular regions of dendritic arbors with implications for information processing within neurons. Cell–cell interactions are widely important for circuit wiring; however, their role in subcellular specificity is not well understood. We studied the role of axon–axon interactions in precise targeting and subcellular wiring of Drosophila somatosensory circuitry. Axons of nociceptive and gentle touch neurons terminate in adjacent, non-overlapping layers in the central nervous system (CNS). Nociceptor and touch receptor axons synapse onto distinct dendritic regions of a second-order interneuron, the dendrites of which span these layers, forming touch-specific and nociceptive-specific connectivity. We found that nociceptor ablation elicited extension of touch receptor axons and presynapses into the nociceptor recipient region, supporting a role for axon–axon interactions in somatosensory wiring. Conversely, touch receptor ablation did not lead to expansion of nociceptor axons, consistent with unidirectional axon–axon interactions. Live imaging provided evidence for sequential arborization of nociceptive and touch neuron axons in the CNS. We propose that axon–axon interactions and modality-specific timing of axon targeting play key roles in subcellular connection specificity of somatosensory circuitry.