Hybrid neural networks in the mushroom body drive olfactory preference in Drosophila

In Drosophila melanogaster, 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.