Hybrid neural networks in the mushroom body drive olfactory preference in <i>Drosophila</i>

In <i>Drosophila melanogaster</i>, olfactory encoding in the mushroom body (MB) involves thousands of Kenyon cells (KCs) processing inputs from hundreds of projection neurons (PNs). Recent data challenge the notion of random PN-to-KC connectivity, revealing preferential connections between food-related PNs and specific KCs. Our study further uncovers a broader picture-an L-shaped hybrid network, supported by spatial patterning: Food-related PNs diverge across KC classes, whereas pheromone-sensitive PNs converge on γ KCs. α/β KCs specialize in food odors, whereas γ KCs integrate diverse inputs. Such spatial arrangement extends further to the antennal lobe (AL) and lateral horn (LH), shaping a systematic olfactory landscape. Moreover, our functional validations align with computational predictions of KC odor encoding based on the hybrid connectivity, correlating PN-KC activity with behavioral preferences. In addition, our simulations showcase the network's augmented sensitivity and precise discrimination abilities, underscoring the computational benefits of this hybrid architecture in olfactory processing.