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

## TL;DR

Scientists rewired a fly's brain circuit by changing cell-surface proteins, altering how neurons connect and affecting male courtship behavior.

## Contribution

The study identifies a combinatorial code of cell-surface proteins that can respecify synaptic connections in neural circuits.

## Key findings

- Altering CSP combinations in a single olfactory neuron type redirected its synaptic connections to a new neuron type.
- The rewiring increased male-male courtship behavior by changing the odor response of the new partner neuron.
- Three manipulation strategies were generalized to rewire a second neuron type to multiple distinct partners.

## 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 targets1,2, it remains largely unknown how multiple CSPs work together to assemble a functional circuit. Here, we used synaptic partner matching in the Drosophila olfactory circuit3,4 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. To achieve this switch, we deduced a combinatorial code including CSPs that mediate both attractive and repulsive interactions between synaptic partners5,6. 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 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.