2025/03/02 by Cheng Lyu, Zhuoran Li, Chuanyun Xu +2 · 1 voice
Neuroscience · Materials Science · #Neurobiology and Insect Physiology Research #Photochromic and Fluorescence Chemistry #Olfactory and Sensory Function Studies
paper · pdf · doi:10.1101/2025.03.01.640986
Abstract Proper brain function requires the precise assembly of neural circuits during development. Despite the identification of many cell-surface proteins (CSPs) that help guide axons to their targets 1,2 , it remains largely unknown how multiple CSPs work together to assemble a functional circuit. Here, we used synaptic partner matching in the Drosophila olfactory circuit 3,4 to address this question. By systematically altering the combination of differentially expressed CSPs in a single olfactory receptor neuron (ORN) type, which senses a male pheromone that inhibits male-male courtship, we switched its connection from its endogenous postsynaptic projection neuron (PN) type nearly completely to a new PN type that promotes courtship. From this switch, we deduced a combinatorial code including CSPs that mediate both attraction between synaptic partners and repulsion between non-partners 5,6 . The anatomical switch changed the odor response of the new PN partner and markedly increased male-male courtship. We generalized three manipulation strategies from this rewiring— increasing repulsion with the old partner, decreasing repulsion with the new partner, and matching attraction with the new partner—to successfully rewire a second ORN type to multiple distinct PN types. This work demonstrates that manipulating a small set of CSPs is sufficient to respecify synaptic connections, paving ways to explore how neural systems evolve through changes of circuit connectivity.