Rewiring an olfactory circuit by altering the combinatorial code of cell-surface proteins

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Proper brain function depends on precise neural circuit assembly during development.
• Cell-surface proteins (CSPs) guide axons, but their collaborative roles in circuit formation are unclear.

Purpose of the Study:

• To investigate how multiple CSPs cooperate to assemble functional neural circuits.
• To determine if manipulating CSPs can alter synaptic connections and influence behavior.

Main Methods:

• Used synaptic partner matching in the Drosophila olfactory circuit.
• Systematically altered combinations of differentially expressed CSPs in olfactory receptor neurons (ORNs).
• Rewired ORN connections to different projection neuron (PN) types.

Main Results:

• Successfully switched ORN connections by altering CSP combinations, effectively changing neural circuit wiring.
• Identified a combinatorial code of CSPs mediating attractive and repulsive interactions.
• Demonstrated that rewiring altered PN odor response and significantly increased male-male courtship behavior.

Conclusions:

• Manipulating a small set of CSPs is sufficient to respecify synaptic connections.
• This provides a method to explore neural system evolution through altered circuit connectivity.
• Highlights the critical role of CSPs in guiding precise neural wiring for brain function.